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PubMed1983

Antigen presentation by human monocytes: evidence for stimulant processing and requirement for interleukin 1.

We studied the role of stimulant processing and presentation and of IL 1 in monocyte-mediated activation of human lymphoproliferative responses. The effects of two lysosomotropic agents, ammonium chloride and chloroquine, on the capacity of human monocytes to activate T lymphocyte responses to the soluble antigen streptolysin O (SLO) and to the polyclonal stimulant S. aureus protein A (SpA) were investigated. These agents inhibited the presentation of SLO and SpA by human monocytes in a dose-dependent manner. The inhibition occurred if monocytes were treated with ammonium chloride and chloroquine for 1.5 hr, starting only 30 min after exposure to the stimulants, whereas only minimal inhibition occurred when monocytes were treated with the two lysosomotropic compounds 2 hr after pulsing with SLO or SpA. In contrast, cell membrane alloantigen presentation by monocytes in the MLR was not affected by ammonium chloride or chloroquine treatment. Thus, these reversible inhibitors of monocyte phagosome-lysosome functions presumably interfere with intracellular processing of the stimulants but do not seem to interfere with alloantigen presentation at the cell surface. Furthermore, we investigated whether gently fixed monocytes were still capable of passively presenting stimulant or whether active metabolic processes as well as IL 1 were required. We observed that only monocytes treated with paraformaldehyde after SLO or SpA pulsing stimulated a proliferative response by T lymphocytes, provided 50 U/ml of partially purified human IL 1 were added back to cultures. In contrast, monocytes fixed before exposure to SLO or SpA were not able to stimulate T lymphocytes even if supplemented by IL 1. Taken together these data suggest that a finite incubation period is required for human monocytes to become able to present SLO or SpA to T lymphocytes. During this time the soluble stimulants presumably undergo some metabolic process in viable macrophages perhaps at the phagosome-lysosome level, to become recognizable by T lymphocytes.

Ammonium Chloride↗

PubMed1983

Phagocytosis of antibody-sensitized Trypanosoma brucei in vitro by bovine peripheral blood monocytes.

The interaction between bovine peripheral blood monocytes and Trypanosoma brucei organisms in the presence of immune whole serum or specific purified IgM or IgG1 antibodies from infected cattle was investigated. Adherence of antibody-sensitized trypanosomes to freshly isolated monocytes from non-infected animals was not observed, confirming the absence of receptors for IgM and IgG1 on fresh monocytes. After in-vitro cultivation of the monocytes for at least 3 hr, adherence of IgM-sensitized trypanosomes was consistently demonstrable, while the adherence of IgG1-sensitized trypanosomes was not observed until the monocytes had been cultured for 7 days. The adherence of IgM-sensitized trypanosomes occurred in the absence of bovine complement and was Ca++-dependent, indicating that the interaction between sensitized trypanosomes and bovine monocytes was mediated through a specific combining site for monocytes in the Fc region of the IgM molecule rather than through a C3b receptor. In contrast to the monocytes from uninfected animals, freshly isolated peripheral blood monocytes from T. brucei- or T. congolense-infected cattle were capable of binding IgM- or IgG1-sensitized trypanosomes after only 30 min and 24 hr of in-vitro cultivation, respectively, suggesting that peripheral blood monocytes from infected animals were already in an "activated' state. Electronmicroscopic examination revealed that IgM- or IgG1-sensitized trypanosomes were rapidly engulfed and digested by the monocytes.

Animals↗

PubMed1994

Platelet glycoprotein IV (CD36) deficiency is associated with the absence (type I) or the presence (type II) of glycoprotein IV on monocytes.

Platelet membrane glycoprotein (GP) IV (also called CD36 and GPIIb) deficiency is associated with N(aka)-negative platelets. Using flow-cytometric analysis of cells stained with the monoclonal anti-GPIV antibody OKM5, we have studied the expression of GPIV on the monocytes from 16 healthy Japanese individuals whose platelets were deficient in GPIV. GPIV was absent on the surface of monocytes from 2 platelet GPIV-negative donors (type I), whereas it was present on the monocytes from the remaining 14 platelet GPIV-negative donors (type II). The fluorescent intensity of OKM5-stained type II monocytes was significantly (P < .05) lower than that of normal monocytes derived from platelet GPIV-positive donors, suggesting that the expression of GPIV on the type II monocytes is also abnormally regulated as compared with that on normal monocytes. OKM5 induced an oxidative burst in the type II monocytes as well as in the normal monocytes, but it failed to induce it in the type I monocytes. Because the 2 individuals with the type I deficiency have been healthy and exhibited no immunologic problems, GPIV appears to be not essential for the normal physiologic functions of monocytes. An anti-GPIV antibody was detected in the serum from one of the type I GPIV-deficient women, who had never received any blood transfusions but had given birth to three apparently healthy children. These results suggest that type I GPIV-deficient individuals may be at risk of developing an anti-GPIV isoantibody upon blood transfusion or pregnancy.

Antibodies↗

PubMed1993

Cell cycle specific effects of tumor necrosis factor alpha in monocyte mediated leukemic cell death and the role of beta 2-integrins.

Human monocytes are involved in host defense against neoplastic cells. In view of cellular immunotherapy with cytotoxic monocytes in minimal residual disease of acute myeloid leukemia we have studied the role of monocytes in cell cycle dependent leukemic cell death of U937, THP-1, and HL-60 cells in vitro. Leukemic cells separated in G1 of the cell cycle by countercurrent centrifugal elutriation were highly susceptible to monocyte mediated cytotoxicity, whereas cells in S and G2-M were less sensitive or completely resistant as compared to unfractionated control cells. HL-60 cells resistant to cytotoxic monocytes became sensitive to monocyte mediated cytotoxicity upon differentiation induction with 1,25-dihydroxyvitamin D3 which paralleled an accumulation of cells in G1 of the cell cycle. The differences in susceptibility of cell phase separated populations to monocyte mediated cytotoxicity paralleled differences in sensitivity to the cytotoxic effects of tumor necrosis factor alpha, as secreted by gamma-interferon activated monocytes. Furthermore, monocyte mediated cytotoxicity was markedly inhibited in the presence of anti-CD11/CD18 monoclonal antibodies recognizing the alpha and beta chains of the beta 2-integrin adhesion proteins. By fluorescence activated cell sorter immunofluorescence a marked increase in mean fluorescence density of the beta 2-integrins could be demonstrated on cells in G1 of the cell cycle as compared to unseparated leukemic cells. A decrease in mean fluorescence density was shown for cells in G2-M. By blocking experiments with anti-CD11/CD18 monoclonal antibodies, the differences in mean fluorescence density were functionally relevant since cells in G1 were shown to be the most sensitive cells to beta 2-integrin dependent monocyte mediated cytotoxicity. In conclusion these data show that differences in sensitivity to tumor necrosis factor and in the expression of beta 2-integrins may play a central role in cell cycle dependent monocyte mediated antileukemic activity.

Antibodies, Monoclonal↗

PubMedDate not supplied

Prothymosin alpha augments deficient antitumor activity of monocytes from melanoma patients in vitro.

Human peripheral blood monocytes derived from normal donors, melanoma patients (MP) before and after chemotherapy (MPa) were assayed for their capacity to inhibit SK-MEL-28 melanoma cell growth in vitro; in addition, growth modulating effects by prothymosin alpha 1 (ProTa) were studied. After preincubation with or without ProTa for 1 day, monocytes were cultured in the absence or presence of interferon-gamma (rIFN-gamma) for a further day, and after cocultivation with SK-MEL-28 melanoma cells for 3 days monocyte/macrophage-mediated tumoristatic activity was determined employing the microculture tetrazolium (MTT) assay. The level of baseline growth inhibitory activity of unstimulated MP and MPa monocytes was 22% and 15%, respectively, and was significantly lower (p < 0.001) than that of normal monocytes (35%). The stimulation of monocytes/macrophages by rIFN-gamma greatly elevated the mean of their antitumor activity up to 44%, 49% and 58% in the group of MP, MPa and normal donors, respectively. ProTa significantly increased the level of monocyte-mediated growth inhibition of MP and normal donors, when it was applied alone or in combination with rIFN-gamma. Monocytes of MP at early stages (I and II) of their disease, when incubated with rIFN-gamma, showed a higher increase in tumoristatic activity than at stage III and tended to be the most susceptible to preincubation with ProTa followed by rIFN-gamma activation. However, on average tumoristatic activity of MP/MPa monocytes was significantly lower compared with that of normal monocytes, when activated with rIFN-gamma or ProTa alone or combined. Moreover, no effects on TNF-alpha secretion of MP/MPa monocytes were found by ProTa and/or rIFN-gamma, whereas TNF-alpha levels from normal monocytes were significantly increased by the two stimuli. These results indicate that monocyte disorders in melanoma patients may be partially normalized by ProTa.

Adult↗

PubMed1995

Enhanced production of TGF-beta by blood monocytes from patients with active tuberculosis and presence of TGF-beta in tuberculous granulomatous lung lesions.

The expression of TGF-beta, a molecule that affects both immune responsiveness and wound healing, was examined in blood monocytes and granulomatous lesions from patients with active pulmonary tuberculosis. The spontaneous release of TGF-beta was higher in culture supernatants of monocytes from patients as compared with those of healthy subjects by an ELISA (p < 0.0005). TGF-beta activity was also confirmed in a bioassay in supernatants from patients. Next, freshly isolated monocytes from patients with tuberculosis and matched subjects were examined for TGF-beta activity. Cytosmears of monocytes were stained with an Ab against TGF-beta 1 (anti-LC) or isotype-specific Ab by using an alkaline-phosphatase anti-alkaline phosphatase method. In contrast to monocytes from healthy individuals, 60 to 70% of monocytes from patients demonstrated cytoplasmic staining for TGF-beta (n = 3). Upon hypotonic lysis, monocytes from patients with tuberculosis contained immunoreactive TGF-beta (n = 3). By Northern blot analysis, monocytes from three of seven patients with tuberculosis had increased expression of TGF-beta mRNA as compared with concurrently examined monocytes from healthy subjects. Within the granulomas of lung sections from two patients with untreated tuberculosis, TGF-beta immunoreactivity was identified in the Langhan's giant cells mainly and to a lesser extent the epithelioid cells using anti-LC Ab and the peroxidase-anti-peroxidase technique. Thus, both blood monocytes and lung granuloma macrophages from patients with active tuberculosis express TGF-beta. Excess activity of this cytokine in blood monocytes may underlie the depressed T cell responses of patients with tuberculosis. Moreover, within the infected tissues excess TGF-beta activity may interfere with anti-mycobacterial mechanisms and effective granuloma formation.

Gene Expression↗

PubMed1996

Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1.

Treatment of human monocytes with vascular endothelial growth factor (VEGF) isolated from tumor cell supernatants was reported to induce monocyte activation and migration. In this study we show that recombinant human VEGF165, and VEGF121 had a maximal effect on human monocyte migration at 65 to 250 pmol/L. Chemotactic activity of VEGF165 was inhibited by a specific antiserum against VEGF, by heat treatment of VEGF165, and by protein kinase inhibitors. In addition, we could show that VEGF-stimulated monocyte migration is mediated by a pertussis toxin-sensitive GTP-binding protein. Placenta growth factor (PlGF152), a heparin-binding growth factor related to VEGF, was also chemotactic for monocytes at concentrations between 2.5 and 25 pmol/L. In accordance with these findings, human monocytes showed specific and saturable binding for 125I-VEGF165 (half-maximal binding at 1 to 1.5 nmol/L). Using Northern blot analysis, we further could show that human monocytes express only the gene for the VEGF receptor type, flt-1, but not for the second known VEGF receptor, KDR. Resting monocytes expressed low levels of flt-1 gene only. Brief exposure (2 to 4 hours) of human monocytes to lipopolysaccharide, a prototypic monocyte activator, led to a significant upregulation of the flt-1 mRNA level. The results presented here suggest that monocyte chemotaxis in response to VEGF and most likely to PlGF152 is mediated by flt-1 and thus show a possible function for the VEGF-receptor flt-1.

Binding, Competitive↗

PubMed1997

Plasmin is a potent and specific chemoattractant for human peripheral monocytes acting via a cyclic guanosine monophosphate-dependent pathway.

We have previously reported that the serine protease plasmin generated during contact activation of human plasma triggers biosynthesis of leukotrienes (LTs) in human peripheral monocytes (PMs), but not in polymorphonuclear neutrophils (PMNs). We now show that purified plasmin acts as a potent chemoattractant on human monocytes, but not on PMNs. Human plasmin or plasminogen activated with urokinase, but not active site-blocked plasmin or plasminogen, elicited monocyte migration across polycarbonate membranes. Similarly, stimulation of monocytes with plasmin, but not with active site-blocked plasmin or plasminogen, induced actin polymerization. As assessed by checkerboard analysis, the plasmin-mediated monocyte locomotion was a true chemotaxis. The plasmin-induced chemotactic response was inhibited by the lysine analog trans-4-(aminomethyl)cyclohexane-1-carboxylic acid (t-AMCA), which prevents binding of plasmin/ogen to the appropriate membrane binding sites. In addition, active site-blocked plasmin inhibited monocyte migration triggered by active plasmin. Further, plasmin-induced monocyte chemotaxis was inhibited by pertussis toxin (PTX) and 1-O-hexadecyl-2-O-methyl-rac-glycerol (HMG) and chelerythrine, two structurally unrelated inhibitors of protein kinase C (PKC). Plasmin, but not active site-blocked plasmin or plasminogen, triggered formation of cyclic guanosine monophosphate (cGMP) in monocytes. LY83583, an inhibitor of soluble guanylyl cyclase, inhibited both plasmin-induced cGMP formation and the chemotactic response. The latter effect could be antagonized by 8-bromo-cGMP. In addition, KT5823 and (Rp)-8-(p-chlorophenylthio)guanosine-3',5'-cyclic monophosphorothioate [(Rp)-8-pCPT-cGMPs], two structurally unrelated inhibitors of cGMP-dependent protein kinase, inhibited plasmin-mediated monocyte chemotaxis. Thus, beyond being a stimulus for lipid mediator release, plasmin is a potent and specific chemoattractant for human monocytes acting via a cGMP-dependent mechanism. Therefore, plasmin represents a proinflammatory activator for human monocytes.

Alkaloids↗

PubMed1998

Neutrophils and monocytes from subjects with the Mediterranean G6PD variant: effect of Plasmodium falciparum hemozoin on G6PD activity, oxidative burst and cytokine production.

Glucose 6-phosphate dehydrogenase (G6PD) activity and oxidative burst were measured in neutrophils and monocytes from five, hemizygous, G6PD-deficient (Mediterranean variant) individuals and five normal controls. Additionally, tumor necrosis factor (TNF), interleukin-10 (IL-10), interleukin-12 (IL-12) release and phagocytosis of the malarial pigment hemozoin or opsonized erythrocytes (RBC) were measured in monocytes recovered from G6PD-deficient and normal individuals. G6PD activity was significantly lower in "deficient monocytes" (38% residual activity, p = 0.01) and not significantly different in "deficient neutrophils" (79% residual activity, p = 0.83) compared to homologous leukocytes recovered from normal controls. Oxidative burst was not significantly different in "deficient" versus "normal" neutrophils and monocytes. Previous phagocytosis of hemozoin decreased the phorbol ester induced oxidative burst in "deficient" and "normal" monocytes but not in neutrophils. Phagocytosis of hemozoin and RBC strongly stimulated cytokine production. With the exception of IL-10, the cytokine production pattern was comparable in "deficient" versus "normal" cells. Incubation with high concentrations of hemozoin (equivalent to 300 RBC per monocyte) strongly stimulated TNF production. Lipopolysaccharide (LPS) had an additive effect on TNF production induced by hemozoin or opsonized RBC. IL-12 production was induced only by the presence of large amounts of hemozoin. IL-10 production was increased in normal monocytes incubated with RBC or hemozoin. LPS increased IL-10 production significantly in monocytes incubated with RBC or low amounts of hemozoin (equivalent to 30 RBC per monocyte), but had no effect when given alone or in conjunction with high concentrations of hemozoin. Interestingly, deficient monocytes produced less IL-10 than normal cells under these conditions. In conclusion, except for IL-10 production, we did not find major functional differences between neutrophils and monocytes from individuals with or without the Mediterranean G6PD mutation.

Animals↗

PubMed2000

Human monocyte adhesion and activation on crystalline polymers with different morphology and wettability in vitro.

This study evaluated the effects of crystalline polyamide (Nylon-66), poly(ethylene-co-vinyl alcohol) (PEVA), and poly(vinylidene fluoride) (PVDF) polymers with nonporous and porous morphologies on the ability of monocytes to adhere and subsequently activate to produce IL-1beta, IL-6, and tumor necrosis factor alpha. The results indicated monocyte adhesion and activation on a material might differ to a great extent, depending on the surface morphology and wettability. As the polymer wettability increases, the ability of monocytes to adhere increases but the ability to produce cytokines decreases. Similarly, these polymers, when prepared with porous surfaces, enhance monocyte adhesion but suppress monocyte release of cytokines. Therefore, the hydrophobic PVDF with a nonporous surface stimulates the most activity in adherent monocytes but shows the greatest inhibition of monocyte adhesion when compared with all of the other membranes. In contrast, the hydrophilic Nylon-66, which has a porous surface, is a relatively better substrate for this work. Therefore, monocyte behavior on a biomaterial may be influenced by a specific surface property. Based on this result, we propose that monocyte adhesion is regulated by a different mechanism than monocyte activation. Consequently, the generation of cytokines by monocytes is not proportional to the number of cells adherent to the surface.

Adult↗

PubMed2001

Interaction of monocytes from patients with psoriatic arthritis with cultured microvascular endothelial cells.

The aim of this study was to investigate the interaction of monocytes of the peripheral blood of patients with psoriatic arthritis with cultured human dermal microvascular endothelial cells (HDMEC) compared to monocytes from control persons. The surface expression of adhesion molecules (ADM) and other cell surface molecules in psoriatic arthritis and control monocytes was investigated by quantitative flow cytometry. The receptor densities of these molecules were determined in terms of monoclonal antibody (mAb) binding sites. Cocultivation experiments including peripheral blood mononuclear cells and HDMEC were performed to determine the adhesion to and transmigration through activated or resting endothelial cell monolayers. In order to achieve optimal responses of cellular functions, activation for adhesion experiments was induced by lipopolysaccharide (LPS), while in transmigration experiments the endothelial cells were activated by TNF-alpha. For transendothelial migration studies HDMEC cultivated on collagen gels were used. In the supernatants of cocultivated cells the cytokines IL-6 and IL-8 were determined by ELISA. A significantly reduced expression of CD11b in nonactivated psoriatic arthritis peripheral blood monocytes compared to control monocytes was verified (mean number of adhesion molecules/cell: 33,756 +/- 10,138 vs 61,023 +/- 6925). In agreement with these findings, adhesion to, as well as transendothelial migration through, activated HDMEC was found to be significantly reduced in psoriatic arthritis monocytes. Transendothelial migration engendered an enrichment of monocytes in the migrated cell fraction for both control and psoriatic arthritis peripheral blood mononuclear cells. The activation of HDMEC by LPS induced a highly significantly enhanced cytokine release for IL-6 and IL-8, irrespective of the origin of monocytes (psoriatic arthritis vs. controls). However, IL-8 production in the supernatants of nonactivated monocytes/HDMEC cocultures was significantly reduced in the case of monocytes from psoriatic arthritis patients (6650 +/- 2489.32 pg/ml) vs 9280.00 +/- 3209.51 pg/ml in control patients. Impaired adhesion as well as transendothelial migration of monocytes derived from peripheral blood of psoriatic arthritis patients can be explained by the reduced expression of adhesion molecules MAC-1 (CD11b/CD18) at the surface of monocytes. The reduced IL-8 production also corresponds to a diminished cellular interaction under nonflow conditions. These results support the view that there are systemic immunological alterations in psoriatic arthritis patients.

Adult↗

PubMed2000

Monocyte chemoattractant protein-1 is a mediator of acute excitotoxic injury in neonatal rat brain.

Monocyte chemoattractant protein-1 is a chemokine with potent monocyte activating and chemotactic effects. Monocyte chemoattractant protein-1 gene and protein expression is rapidly up-regulated in response to a variety of acute and chronic central nervous system disorders. The activation and recruitment of microglia and monocytes into areas of inflammation may play a critical role in the pathogenesis of acute brain injury. Monocyte chemoattractant protein-1 could be a pathophysiologically important mediator of the microglial and monocyte responses in the brain. Using a well-characterized model of acute excitotoxic brain injury in neonatal rats, experiments were designed to evaluate whether monocyte chemoattractant protein-1 plays a role in the progression of tissue damage. Direct co-administration of recombinant monocyte chemoattractant protein-1 with the excitotoxin N-methyl-D-aspartate exacerbated injury, both in the striatum and in the hippocampus, by 55% and 167%, respectively. Complementary experiments to determine the effect of functional inhibition of monocyte chemoattractant protein-1, using an anti-monocyte chemoattractant protein-1-neutralizing antibody, revealed that co-administration of the antibody with N-methyl-D-aspartate attenuated tissue injury in the striatum and hippocampus by 57% and 39%, respectively.Together, these data suggest that monocyte chemoattractant protein-1 is a mediator of acute excitotoxic brain injury in neonatal rats and that inflammatory mechanisms contribute significantly to the pathogenesis of acute neonatal brain injury. Whether chemokines are pathophysiologically relevant mediators of neuronal injury in human neonates remains to be determined.

Acute Disease↗

PubMed1996

Regulation of newborn and adult monocytes by PGE2: evidence of comparable differentiation status.

PGE2, which is produced in large amounts by monocytes, is considered to be an important autocrine factor in the regulation of the immune response. Altered sensitivity to PGE2 is known to reflect the differentiation status of monocytes/macrophages. Since newborn monocytes are thought to be less differentiated than adult peripheral blood monocytes, this study was designed to determine whether the diminished newborn monocyte function, relative to adult peripheral blood monocytes, might be the result of an altered autocrine responsiveness to PGE2. Phosphodiesterase activity as well as cAMP and TNF alpha levels in response to PGE2 were measured in newborn and adult monocytes, as an index of sensitivity to PGE2. Basal intracellular cAMP levels were reduced in cord monocytes compared with adult monocytes. Addition of increasing concentrations of PGE2 (10M(-10)-10M-6) caused similar fold increases in intracellular levels of cAMP for both populations. Lipopolysaccharide-induced TNF alpha production was significantly reduced in a similar fashion for both cord and adult monocytes at high (> or = 10(-7)M) PGE2 concentration. Phosphodiesterase activity was comparable in lysates from both populations. This study shows that PGE2 does not differentially influence newborn and adult monocyte responses and therefore that the diminished functional abilities of newborn monocytes is not due to altered autocrine responsiveness.

Adult↗

PubMed2005

[Atorvastatin reduces the expression of COX-2 mRNA in peripheral blood monocytes in patients with acute myocardial infarction and modulates the early inflammatory response].

OBJECTIVE: To measure the effect of atorvastatin on COX-2 expression in monocytes in patients with acute myocardial infarction (AMI). METHODS: Forty patients with AMI (AMI group) and 18 patients with stable coronary heart disease (control group) were enrolled, and patients with AMI were randomly given routine therapy (n = 20) and routine therapy plus atorvastatin (20 mg/day, n = 20) for a week. Peripheral blood monocytes for each participant including patients with AMI were isolated and cultured for 24 hours. During the culture, monocytes in patients with pretreatment AMI were incubated with celecoxib in different concentration (0, 0.1, 1 and 10 micromol/L). COX-2 mRNA expression in monocytes was measured by reverse transcription polymerase chain reaction (RT-PCR); concentrations of interleukin-6 (IL-6) in supernatant from monocytes and plasma hs-CRP levels were measured by using enzyme-linked immunosorbent assay (ELISA). RESULTS: COX-2 expression in monocytes in patients with AMI (0.92 +/- 0.13) was significantly higher than that in the control subjects (0.19 +/- 0.08), and decreased by 66% after atorvastatin (compared with that on routine therapy, P < 0.05); IL-6 secretions of monocytes in the AMI group (204.8 +/- 45.6 ng/L) increased dramatically compared with those in the control group (40.9 +/- 1.2 ng/L, P < 0.05), and reduced dramatically by 58% when incubated with 10 micromol/L celecoxib (P < 0.05) in a concentration-dependent manner; plasma levels of CRP in the AMI group (43.3 +/- 14.9 mg/L) significantly increased compared with those in the control group (1.7 +/- 0.8 mg/L), and reduced by 62% after atorvastatin (compared with those in the routine therapy group, P < 0.05). COX-2 expression in monocytes in the AMI group was positively correlated with both secretions of IL-6 and plasma level of CRP (r = 0.636 and 0.662, respectively, both P < 0.05). CONCLUSIONS: There is an inflammatory activation in peripheral blood monocytes in patients with early AMI, and the monocytes-derived COX-2 may play an important role in promoting early inflammatory process. Atorvastatin may decrease COX-2 expression in peripheral blood monocytes in patients with AMI and cyclooxygenase-dependent pathway might be correlated with the anti-inflammation mechanism of statin.

Aged↗

PubMed1987

Colony-stimulating factor-induced monocyte survival and differentiation into macrophages in serum-free cultures.

The role of mononuclear phagocyte-specific colony-stimulating factor (CSF-1) in human monocyte to macrophage differentiation was investigated. The addition of 1000 U/ml of CSF-1 to serum-free monocyte cultures resulted in monocyte survival comparable to that in cultures containing 5% AB serum, whereas cells in serum- and CSF-1-free medium lost their viability in 3 to 5 days. The requirement for CSF-1 coincided with the time (40 to 64 hr of culture) when the major changes in morphology and biochemical function took place in monocytes undergoing differentiation into macrophages. If CSF-1 was removed from the cultures before this time, death of the monocytes resulted. In cultures containing CSF-1, as in serum containing cultures, the lysosomal enzyme acid phosphatase was enhanced 10- to 20-fold by day 4 to 5. Superoxide production in response to phorbol myristic acetate was maintained in CSF-1 cultured monocytes, but declined with time in monocytes cultured in serum. The expression of monocyte-macrophage antigens p150.95 (LeuM5), OKM1, LeuM3, Fc receptors (32.2), and HLA-DR had increased in CSF-1 containing cultures at day 4. When antigen expression was analyzed at day 2 to 3, when cell size and 90 degrees scatter characteristics were still identical to control serum-free cultures, only p150.95, HLA-DR and FcR expression were enhanced by CSF-1. Low amounts of lipopolysaccharide (0.1 ng/ml) were found to enhance monocyte survival in the absence of added CSF-1. Lipopolysaccharide-containing cultures were found to produce CSF-1 (up to 450 U/ml, as detected by radioimmunoassay). Lipopolysaccharide (1 microgram/ml), however, did not induce enhanced expression of the maturation-related antigens. Based on these observations we conclude that CSF-1 is enhancing human monocyte survival and is involved in the events leading to the differentiation of monocytes into macrophages.

Acid Phosphatase↗

PubMed1987

Mechanisms of HLA-DR antigen expression in phytohemagglutinin-activated T cells in man. Requirement of T cell recognition of self HLA-DR antigen expressed on the surface of monocytes.

Signals required for expression of HLA-DR (DR) antigen in phytohemagglutinin (PHA)-activated human peripheral blood T cells were examined. T cells were purified by a four-step procedure, which included depletion of glass-adherent cells, 53% Percoll gradient centrifugation, nylon wool column passage, and treatment with mouse monoclonal antibodies directed to human HLA-DR antigen and Leu M1 antigen plus complement. Purified T cells responded poorly to PHA but with the combination stimuli of PHA and recombinant human interleukin 2 (rIL-2), resting T cells proliferated as well as T cells cultured with 10% monocytes and PHA. But well proliferated T cells in the absence of monocytes expressed very poor DR antigen after 7 to 8 days of culture. DR expression of T cells was restored by the addition of 10% monocytes. Allogeneic monocytes also helped proliferative responses of PHA-activated T cells but did not help the expression of DR antigen. These results suggested that signals required for T cell proliferation (PHA and rIL-2) were not sufficient for DR expression in this system and further monocytes were essentially required in a HLA-restricted manner. In the next experiment, we examined the role of membrane molecules in monocytes for transmission of signals that induce activated T cells to express DR antigen. Autologous monocytes were fixed with 1% paraformaldehyde and added to T cells in the presence of PHA and rIL-2. Fixed monocytes could help DR antigen expression of PHA-activated T cells as well as viable monocytes. But when fixed monocytes were pretreated with anti-HLA-DR monoclonal antibody, they could not help DR expression of T cells any longer. These results suggested that for the expression of DR antigen, PHA-activated T cells had to first recognize self DR antigen expressed on the surface of monocytes before proliferation occurred.

Antibodies, Monoclonal↗

PubMed1975

The fungicidal mechanisms of human monocytes. I. Evidence for myeloperoxidase-linked and myeloperoxidase-independent candidacidal mechanisms.

We tested the ability of human peripheral blood monocytes to kill Candida albicans and Candida parapsilosis. Evidence that multiple fungicidal mechanisms operate in normla monocytes was found. Normal monocytes ingested and killed viable C. albicans, and could iodinate heat-killed C. albicans. Both functions were defective in monocytes from subjects with myeloperoxidase deficiency or chronic granulomatous disease. Methimazole, isoniazid, and aminotriazole inhibited iodination by normal monocytes without impairing their ability to kill C. albicans, indicating that iodination was not essential to the myeloperoxidase-hydrogen peroxide-mediated fungicidal system of the monocyte. C. parapsilosis, an organism killed with supranormal efficacy by monocytes from a patient with hereditary myeloperoxidase deficiency, was selected to examine the myeloperoxidase-independent fungicidal mechanisms of monocytes. Monocytes were obtained from the blood of normal or leukemic subjects and homogenized in 0.34 M sucrose to yield fractions rich in cytoplasmic granules. These fractions were extracted with 0.01 M citric acid and the soluble components were separated by micropreparative polyacrylamide electrophoresis. Monocytes were found to contain cationic proteins, other than myeloperoxidase, that kill C. parapsilosis in vitro.

Anti-Inflammatory Agents↗

PubMed1988

Mechanisms of altered monocyte prostaglandin E2 production in severely injured patients.

Monocytes from immunosuppressed trauma (11 patients) and burn (12 patients) patients stimulated with muramyl dipeptide, a potent prostaglandin E2 (PGE2) secretagogue, showed twofold greater PGE2 production compared with normal controls or immunocompetent patients. Monocyte plasminogen activator production was markedly depressed and inversely correlated to patients' monocyte hyper PGE2 production. Levels of the PGE2-producing monocyte subset (selected as high-affinity Fc+ receptors) were progressively elevated after injury in immunosuppressed patients, reaching 65% to 80% of the total monocyte population (39% for normal controls). Although early T-suppressor (Ts) lymphocytes did not augment monocyte PGE2 secretion, Ts lymphocytes that appeared late (greater than 12 days after injury), during chronic infection, acted as monocyte PGE2 secretagogues. Posttraumatic increases in monocyte sensitivity to PGE2 secretagogues augmented the numbers of PGE2-secreting monocytes, and the appearance of Ts lymphocytes with PGE2 secretagogue activity may be responsible for elevated monocyte PGE2 production in immunosuppressed trauma patients.

Adult↗