Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MONOCYTES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1989

Lactoferrin decreases monocyte-induced fibroblast production of myeloid colony-stimulating activity by suppressing monocyte release of interleukin-1.

Lactoferrin (Lf) is a negative regulator of myelopoiesis which operates by suppressing the release from mononuclear phagocytes of GM colony-stimulating factor (GM-CSF) or monokines which can then induce the release of GM-CSA from accessory cells. In this study, endotoxin-depleted, purified iron-saturated human Lf was assessed for its effect on the production of interleukin-1 by cultured monocytes and their subsequent effect on colony-stimulating factor release from cultured fibroblasts. Monocytes were grown with or without Lf and Lf that had previously been incubated with monoclonal anti-Lf. The monocyte-conditioned medium was then either assayed for the presence of interleukin-1 (IL-1) with an enzyme-linked immunosorbent assay or for its ability to stimulate fibroblasts to release growth factors for CFU-GM, BFU-E, or CFU-Mix colonies. In the presence of Lf (10(-7) or 10(-8) mol/L), GM colony-stimulating activity (GM-CSA) was suppressed by 31% to 73%, whereas stimulating activities for BFU-E and CFU-mix colony formation were suppressed by 93% to 100%. Antibody to Lf completely abrogated the suppressive effects observed with Lf, whereas antibody to IL-1 ablated the induction by monocyte-conditioned medium of CSA release by fibroblasts. Lf at 10(-7) and 10(-8) mol/L also reduced IL-1 synthesis by cultured monocytes from 60% to 77%. The inhibitory effects of Lf were only observed when Lf was added before adherence of the monocytes for culture. If Lf was added at the time of adherence or after adherence, no suppression was observed. We conclude that the inhibition of GM-CSA production/release by Lf is mediated through inhibition of the synthesis/release of IL-1 by mononuclear phagocytes. This inhibition of IL-1 prevents accessory cells from producing and/or releasing GM-CSA.

Bone Marrow Cells↗
PubMed1986

Monocyte procoagulant inducing factor: a lymphokine involved in the T cell-instructed monocyte procoagulant response to antigen.

A T cell-derived lymphokine couples the recognition of alloantigens by human T inducer cells to monocyte effector procoagulant activity (PCA). This collaborative cellular response results in expression of the functional tissue factor gene product and initiation of the extrinsic coagulation protease cascade as an inflammatory sequelae to the immune response. We now provide initial characterization of this lymphokine, provide evidence that it is a unique lymphokine, and designate it as monocyte procoagulant inducing factor (MPIF). MPIF was produced by alloantigen-stimulated, nylon wool-purified T cells and was not diminished by irradiation. MPIF active supernatants induced PCA in isolated monocytes, and the effect was not modified by the presence of T cells with the responding monocytes, consistent with a direct effect on the monocyte effector cells rather than an indirect effect via an intermediate accessory T cell. Full expression of PCA by monocytes was complete within 4 to 6 hours. MPIF activity in mixed lymphocyte culture (MLC) supernatants (MLC-SN) was stable at pH 2.0 for 24 hr, but was diminished after exposure to pH 10.5 for 30 min. MPIF activity was stable at 56 degrees C but was labile at 63 degrees C or higher. When characterized by chromatography on Sephadex G-100 superfine at either pH 7.2 or 3.6, the activity was recovered in a major discrete peak of about 55,000 daltons, and minor peaks of activity at about 14,000 and greater than 150,000 daltons. There was no correlation between the presence or concentration of INF-gamma, INF-alpha, IL 1, IL 2, GM-CSF, CSF-1, TNF-alpha, TNF-beta (lymphotoxin), or migration inhibitory factor (MIF) with MPIF activity. Each of the previously defined cytokines was analyzed directly for MPIF activity. INF-gamma, INF-alpha, GM-CSF, TNF-alpha, and CSF-1 did not possess MPIF activity over a wide range of concentrations. IL 1 and IL 2 lacked activity at concentrations present in MLC medium positive for MPIF; however, at higher concentrations each demonstrated slight activity. There was a poor correlation between MPIF and MIF activities in MLC-SN, and the content of MIF was insufficient to account for the expressed level of MPIF activity. The lack of identity of these cytokines with MPIF was supported by selected MLC medium that lacked IL 1, IL 2, and MIF and yet contained high MPIF activity. MPIF was additionally distinguished from IL 1, IL 2, and MIF on the basis of separation in Sephadex G-100 superfine.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Coagulation Factors↗
PubMed1978

Antigens in human monocytes. III. Use of monocytes in typing for HLA-D related (DR) antigens.

Monocyte preparations were obtained from the peripheral blood by adherence to plastic dishes. The number of monocytes obtained was significantly greater than the number of B cells recovered from similar samples. Monocytes could be frozen and thawed with relatively little loss in cell numbers or viability. Cytotoxicity tests were performed most reliably at 20 degrees C. Under these conditions, autoantibodies were rare, and normal sera were consistently negative. Serologic reactions obtained with monocytes correlated well with the known specificities of the monocyte panel. Typing results in both normal and diseased populations were similar to results obtained with B lymphocytes. Moreover monocyte cytotoxicity tests were more convenient and easier to read than similar tests performed with B cells.

Arthritis, Rheumatoid↗
PubMed1986

Detection of different interleukin-1 activities in human monocytes and monocytic cell lines.

Culture supernatants from normal human monocytes, monocyte hybrid cell lines, and myelomonoblastic cell lines were tested for human interleukin-1 (IL-1) activity. In the present study, we report the detection of IL-1 secreted by several cell lines of monocyte origin and compare their biological and biochemical characteristics. IL-1 activity was tested by the regular assay of phytohemagglutinin (PHA) response of mouse thymus cells. IL-1 was found to be constitutively secreted by U937 and the M20 cell lines, as well as by three of the monocyte hybrid cell lines. The activity was always augmented following dialysis and did not require the presence of serum for its secretion. We compared the IL-1 activity of the myelomonoblastic M20 and hybrid 1C4 cell lines to that of normal monocytes. We found differences in the kinetics of IL-1 secretion, the pattern of activity following dilution of concentrated supernatants, and augmentation of activity by various inducers. The differences described may be explained by concomitant secretion of IL-1 inhibitory factors, as well as the secretion of activities other than IL-1. Preliminary biochemical analysis showed that all three cell sources tested shared some species of molecules characterized by gel filtration and ion-exchange chromatography. However, some species of molecules expressing IL-1 activity were unique to the cell lines and were not found in normal monocytes.

Animals↗
PubMed1981

The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions.

In a previous publication the author and his co-workers demonstrated that atherosclerotic lesion development in the aorta of hypercholesterolemic pigs was preceded by intimal penetration of blood-borne mononuclear cells, and that medial smooth muscle cells were not involved in the formation of early fatty lesions in this model. The current study shows that aortic arch lesions do not progress beyond the fatty cell lesion stage for up to 30 weeks of a moderate cholesterol/lard diet, although they become more extensive in area. Mononuclear cells were found adherent to the endothelium, in endothelial junctions, and in the intima during this period, and were ultrastructurally identified as monocytes by the presence of peroxidase-positive granules (peroxisomes) in their cytoplasm. In addition, lesion areas with nonspecific esterase activity correlated well with Sudan IV staining. Intimal monocytes and altered intimal monocytes with an enlarged cytoplasm and containing a few lipid droplets were both shown to be phagocytic by their uptake of ferritin, which had penetrated the intima after intravenous injection. Circulating monocytes and those adherent to the endothelial surface did not contain ferritin in these animals. The results indicate that blood mononuclear cells associated with lesion formation in this model are, in fact, monocytes, which subsequently undergo transformation into macrophage foam cells in fatty streak lesions. The absence of medial cell involvement indicates that monocytes are the major foam cell precursor in these lesions.

Animals↗
PubMed1993

Receptor-activated calcium influx in human monocytes exposed to monocyte chemotactic protein-1 and related cytokines.

Stimulation of human monocytes with monocyte chemotactic protein-1 (MCP-1) resulted in an increase of [Ca2+]i. The [Ca2+]i rise was dependent on external Ca2+, could be reconstituted by the addition of external Ca2+ and was blocked by Ni2+. Agonist-stimulated Ca2+ influx was demonstrated directly by the use of Mn2+: in the presence of extracellular Mn2+, MCP-1 and FMLP stimulated a dose-dependent quench in fluorescence of Fura-2-loaded monocytes. This quench was the result of stimulation of Mn2+ influx and was blocked by Ni2+ and by the Ca2+ channel inhibitor SC38249. Pretreatment of monocytes with verapamil and nifedipine or high depolarizing [K+] had no effect. MCP-1 did not induce production of inositol triphosphate nor turnover of phosphatidylinositol 4,5-biphosphate. Collectively, these results show that MCP-1 does not induce discharge of intracellular stores. This chemokine stimulates divalent cation entry (Ca2+ or Mn2+) by a mechanism independent of changes in [Ca2+]i, unrelated to voltage-dependent Ca2+ channels and presumably involving receptor-activated channels. In addition to MCP-1, also two other members of the chemokine Cys-Cys family, RANTES and MIP-1 alpha, stimulated [Ca2+]i increase. Exposure of human monocytes to either RANTES or MIP-1 alpha, had no effect on a subsequent stimulation by MCP-1. On the contrary, MCP-1 cross-desensitized monocytes for a subsequent stimulation with RANTES and MIP-1 alpha. These results suggest a certain level of receptor sharing among members of the Cys-Cys chemokine family.

Calcium↗
PubMed1994

Cellular binding site and membrane binding proteins for triglyceride-rich lipoproteins in human monocyte-macrophages and THP-1 monocytic cells.

Triglyceride- and cholesterol-rich foam cells derived from monocyte-macrophages are commonly associated with some forms of hypertriglyceridemia. In this report, direct binding studies at 4 degrees C demonstrate that human monocyte-macrophages (HMM) 1-6 days after isolation from blood and human THP-1 monocytic cells, before and up to 7 days after differentiation with phorbol ester, exhibit a high affinity (Kd 3-6 nM), saturable, specific, and apolipoprotein (apo) E-independent binding site for the uptake and degradation of certain triglyceride-rich lipoproteins (TGRLP). Ligand blotting analysis identified two membrane binding proteins (MBP) of apparent molecular weights of 200 and 235 kDa (MBP 200 and MBP 235) in both cell types that share the same ligand specificity as the cellular site and bind hypertriglyceridemic (HTG) VLDL, trypsinized VLDL devoid of apoE (tryp-VLDL), and dietary plasma chylomicrons from normal subjects but not LDL, acetyl LDL, or normal VLDL with high affinity. Neither lipoprotein lipase nor apoE are required for TGRLP binding to the cells or the isolated MBPs. The cellular binding site and the MBPs are expressed at similar levels at all stages of differentiation, unlike the LDL or the acetyl LDL receptor. TGRLP that bind to the MBPs induce rapid, saturable, cellular triglyceride accumulation in monocytes as well as macrophages; normal VLDL does not. In addition, the cellular high affinity binding site and MBP 200 and 235 are not affected by the media sterol content, unlike the LDL receptor. Taken together, these data indicate that human monocyte-macrophages exhibit a high affinity, saturable, specific, apoE- and lipoprotein lipase-independent binding site and membrane binding proteins for TGRLP that differ in expression, specificity, and molecular size from receptors of the LDL receptor gene family or the acetyl LDL receptor. The shared characteristics of the cellular binding site with MBP 200 and MBP 235 suggest that they are candidates for the receptor-mediated, apoE-independent uptake of HTG-VLDL and chylomicrons by monocytes and macrophages and therefore may be involved in foam cell formation.

Animals↗
PubMed1993

Tumour necrosis factor-alpha augments the expression of Fc IgE receptor (Fc epsilon RII/CD23) on human monocytic cell lines and down-regulates interleukin-4-driven Fc epsilon RII expression on monocytes.

We investigated the expression of the low affinity Fc IgE receptor (Fc epsilon RII/CD23) on the human monocytic cell lines U937, THP-1, Mono-Mac-6, and cultured human peripheral blood monocytes under stimulation with human tumour necrosis factor-alpha (TNF-alpha) and other cytokines. Fc epsilon RII was demonstrated by flow cytometry analysis employing the anti-Fc epsilon RII monoclonal antibody 3-5. TNF-alpha alone had a weak but significant stimulating effect on the Fc epsilon RII expression on the cell lines U937 and THP-1, and very modestly on Mono-Mac-6 cells. TNF-alpha strongly synergized with interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). IFN-alpha per se was ineffectual, but was able to increase the TNF-alpha effect. Furthermore, the action of TNF-alpha was slightly augmented by human IL-6. Similar effects were noted with TNF-beta alone or in combination with other cytokines. Interestingly, on human monocytes TNF-alpha weakly reduced the basal level of Fc epsilon RII, and markedly diminished the IL-4-induced Fc epsilon RII expression. Our results indicate that several cytokines may interact in a cytokine network to modulate Fc epsilon RII expression on monocytic cell lines. On human blood monocytes, TNF-alpha, like IFN-gamma or IL-6, counteracts the IL-4-induced Fc epsilon RII expression. These data suggest different regulatory pathways of Fc epsilon RII expression on blood monocytes and myelomonocytic cell lines.

Cell Line↗
PubMed1993

Novel function of C4a anaphylatoxin. Release from monocytes of protein which inhibits monocyte chemotaxis.

The complement C4-derived anaphylatoxin, C4a, possesses a strong chemotaxis inhibitory capacity to blood monocytes at concentrations as low as 10(-16) mol/L. In our study, treatment with carboxypeptidase B to convert it to C4a des Arg77 decreased the inhibitory activity to less than 1/1,000. The extraordinary inhibitory capacity of C4a suggests the presence of an amplification mechanism in this inhibition. Indeed, we found that the conditioned media of peripheral blood mononuclear cells or monocyte/macrophage lineage cell lines (U937 and THP-1 cells) preincubated with 10(-16) mol/L C4a for 5 minutes or more at 37 C possessed the inhibitory capacity 100,000-fold stronger than the original activity of C4a. The monocyte-derived chemotaxis inhibitory factor seemed monocyte-specific. This cell-derived factor was sensitive to treatment with trypsin and chymotrypsin and immunologically distinct from C4a. The apparent molecular size of the monocyte factor was estimated to be approximately 20 kd by gel filtration. These results indicate that C4a anaphylatoxin induces the release from monocytes of a protein with inhibitory activity for monocyte chemotaxis.

Cell Line↗
PubMed1996

Activation and priming of human monocytes by monocyte chemotactic activating factor: cooperation with other inflammatory cytokines and close association between an increase in cytoplasmic free Ca2+ and intracellular acidification.

Both monocyte chemotactic and activating factor (MCAF) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated an increase in cytoplasmic free Ca2+ ([Ca2+]i) and changes in intracellular pH (pHi) in human monocytes in parallel at lower concentrations and stimulated superoxide (O2-) release and changes in transmembrane potential in parallel at higher concentrations. The changes in pHi were characterized by initial rapid acidification followed by sustained alkalinization, and the changes in transmembrane potential were characterized by initial depolarization followed by partial repolarization. The time courses of all responses stimulated by MCAF and FMLP were similar to each other, although the magnitude of all responses was less in MCAF-stimulated cells. MCAF by itself was a very weak stimulus for inducing O2- release. However, MCAF primed monocytes and enhanced O2- release stimulated by FMLP. The priming effect of MCAF was maximal within 5 minutes of preincubation, and the dose-response curves for priming were identical to those for triggering of an increase in [Ca2+]i. Treatment of monocytes with the intracellular Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), abolished not only the increase in [Ca2+]i but also the changes in pHi (both acidification and alkalinization) induced by MCAF or FMLP. MCAF further potentiated FMLP-induced O2- release in tumor necrosis factor (TNF)-, granulocyte-macrophage colony-stimulating factor (GM-CSF)-, or IL-3-primed monocytes. These findings suggest that MCAF, alone or in concert with other cytokines, primes monocytes for enhanced release of 02-, and that MCAF- or FMLP-induced intracellular acidification and alkalinization are closely associated with an increase in [Ca2+]i, but not O2- release.

Adult↗
PubMed1996

The effect of HA, TCP and ALCAP bioceramic capsules on the viability of human monocyte and monocyte derived macrophages.

The relationship between various bioceramics used in surgical implantation and inflammatory cellular response has not been fully elucidated. The objective of this study was to investigate the effect of various biomedical ceramics such as tricalcium phosphate (TCP), hydroxyapatite (HA), and aluminum-calcium-phosphorous oxide (ALCAP) on the adherence and viability of human monocyte and monocyte derived macrophages in vitro. The monocytes were isolated from human peripheral blood and seeded at a density of 5 x 10(5) cells/well according to standard laboratory procedures. Cells were considered macrophages after remaining in culture for 24 hours. Cells were then plated in each microtiter well loaded with ceramic capsules (HA, TCP and ALCAP) and buffered control. At the end of 1, 2, 3, and 7 days the viability and cell number of monocyte or monocyte derived macrophages were determined using an established assay. Cell number was determined in control wells with known amounts of cell number, a standard curve was generated by plotting absorbance units versus cell number. Biochemical analysis was performed on the aliquots obtained from the experimental and control wells at the end of each phase of the investigation. The data from this experiment suggest that: (I) monocytes and macrophages are capable of adhering to the surface of HA, TCP and ALCAP in an in vitro environment for over a 7 day period. (II) Long term incubation of ceramic capsules with macrophages revealed that the cells experienced gradual disassociation phenomenon with a greater number of cell detachment seen in the ALCAP contained wells. (III) SEM analysis of representative capsules demonstrated that there is an increase in the number of micropores on the surface of the materials after contacting a cellular environment. This observation suggest that the material surface has been modified (TCP > HA = ALCAP). (IV) Biochemical analysis of aliquots at the end of each phase showed a significant change (P < 0.05) in the activity of catalase and superoxide dismutase (SOD). Information obtained from this study provided new insights on the interrelationship between bioceramics and the possible cell response during chronic inflammation at the site of implantation.

Aluminum Oxide↗
PubMed1996

T helper 2 cytokines differently regulate monocyte chemoattractant protein-1 production by human peripheral blood monocytes and alveolar macrophages.

Th2 cytokines, such as IL-4, IL-10, and IL-13, suppress proinflammatory cytokine production by monocytes/macrophages. Since monocyte chemoattractant protein-1 (MCP-1) is presumed to play an important role in monocyte recruitment and activation during inflammatory and immune responses, we examined here the effects of these Th2 cytokines on MCP-1 production by human blood monocytes and alveolar macrophages. Unstimulated, highly purified blood monocytes did not produce MCP-1 spontaneously, while LPS treatment induced the production of MCP-1 and its mRNA expression. All Th2 cytokines tested suppressed LPS-induced MCP-1 production and its mRNA expression, although the suppressive effect of IL-13 was weaker than that of IL-4 or IL-10. In contrast, IL-10, but neither IL-4 nor IL-13, induced unstimulated peripheral blood monocytes to produce biologically active MCP-1 protein within 4 h, reaching a maximal level at 12 h. IL-10-induced MCP-1 production was reduced by pretreatment of IL-10 with anti-IL-10 Ab, negating the involvement of contaminated endotoxin. Moreover, IL-10 induced MCP-1 mRNA expression in unstimulated monocytes, independent of de novo protein synthesis. Furthermore, human alveolar macrophages produced MCP-1 spontaneously, and the production was inhibited by IL-4 or IL-13, but was augmented by IL-10. These findings suggest that IL-10 regulates MCP-1 production by monocytes/macrophages in a different way from other Th2 cytokines, such as IL-4 and IL-13, and contributes to host defense responses.

Cells, Cultured↗
PubMed1997

Transgenic monocyte chemoattractant protein-1 (MCP-1) in pancreatic islets produces monocyte-rich insulitis without diabetes: abrogation by a second transgene expressing systemic MCP-1.

Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that attracts monocytes and T lymphocytes in vitro; however, its in vivo functions are poorly understood. To address this question, we constructed transgenic mice expressing MCP-1 controlled by an insulin promoter. These mice developed a chronic insulitic infiltrate composed of F4/80+ monocytes with minor populations of CD4+, CD8+, and B220+ cells. Despite persistent transgene expression, the insulitis never progressed, and blood glucose levels remained normal. Thus, MCP-1 alone is sufficient to elicit a monocytic infiltrate, but not to activate elicited cells. These results differ from those obtained with another transgenic model using the mouse mammary tumor virus long terminal repeat, in which mice expressed substantial MCP-1 in several organs but had no infiltrates. However, mice expressing both transgenes had minimal insulitis, indicating that high systemic levels of MCP-1 prevented monocytes from responding to local MCP-1. Thus, the ability of MCP-1 to elicit monocytic infiltration depends on its being expressed at low levels in an anatomically restricted area.

Animals↗
PubMed1997

Interleukin-15 (IL-15) induces IL-8 and monocyte chemotactic protein 1 production in human monocytes.

Interleukin-15 (IL-15) is a recently characterized cytokine that shares many biological activities with IL-2 and interacts with the beta and gamma components of the IL-2 receptor. Unlike IL-2, which is secreted only by T cells, IL-15 is expressed preferentially by nonlymphoid tissues, epithelial, and fibroblast cell lines and by activated monocytes/macrophages. High concentrations of IL-15 have been shown in inflamed joints of rheumatoid arthritis patients, suggesting a role for IL-15 in inflammatory diseases where there is recruitment of leukocytes. Although monocytes have been shown to bind IL-15, its effects on these cells are not defined. In this report we show that supernatants of monocytes treated with IL-15-contained chemotactic activity for neutrophils and monocytes which was neutralized by anti-IL-8 or by anti-monocyte chemotactic protein 1 (MCP-1) antibodies, respectively. Secretion of IL-8 and MCP-1 proteins is detectable by enzyme-linked immunosorbent assay as early as 6 hours after stimulation with IL-15. Production of the two chemokines is correlated with induction by IL-15 of mRNA expression in monocytes. In addition, IL-8 and MCP-1 induction by IL-15 is differently regulated by interferon-gamma (IFN-gamma) and IL-4. IFN-gamma inhibited IL-15-induced IL-8 secretion, but synergized with IL-15 in MCP-1 induction; whereas IL-4 inhibited both IL-8 and MCP-1 induction by IL-15. These results show that IL-15 can stimulate monocytes to produce chemokines that cause inflammatory cell accumulation. Thus, IL-15 locally produced at sites of inflammation may play a pivotal role in the regulation of the leukocyte infiltrate.

Cells, Cultured↗
PubMed2004

A shift in the balance of inhibitory and activating Fcgamma receptors on monocytes toward the inhibitory Fcgamma receptor IIb is associated with prevention of monocyte activation in rheumatoid arthritis.

OBJECTIVE: To assess surface expression of the inhibitory receptor for IgG (Fcgamma receptor IIb [FcgammaRIIb]) in relation to activating FcgammaR on monocyte/macrophages from patients with rheumatoid arthritis (RA) and healthy controls and to study the influence of proinflammatory and antiinflammatory cytokines on the balance of inhibitory and activating FcgammaR. METHODS: Using a combination of genotyping and phenotyping, surface expression of FcgammaRIIb on monocytes from healthy control subjects and RA patients was demonstrated. Expression of FcgammaR on CD14+ monocytes was assessed by flow cytometry. Regulation of inhibitory and activating FcgammaR on monocytes by proinflammatory (interferon-gamma [IFNgamma], tumor necrosis factor alpha [TNFalpha]) and antiinflammatory (interleukin-4 [IL-4], IL-10) cytokines was studied. A functional change in cytokine-modulated monocytes was assessed in secondary cultures by their ability to produce TNFalpha upon FcgammaR crosslinking by IgG. RESULTS: Monocytes from healthy controls and RA patients expressed FcgammaRIIb at similar levels, in contrast to the higher levels of activating FcgammaRI and FcgammaRIIa in RA patients. The regulation of FcgammaR expression was comparable for patients and controls. IFNgamma selectively up-regulated FcgammaRI. TNFalpha down-regulated expression of FcgammaRIIb and the activating FcgammaR, whereas IL-10 up-regulated expression of monocytic FcgammaRIIb and all activating FcgammaR. Increased or sustained levels of activating over inhibitory FcgammaR induced by IFNgamma, TNFalpha, and IL-10 alone were associated with enhanced IgG-triggered TNFalpha production. In contrast, IL-4 and, more specifically, IL-4 plus IL-10 altered the FcgammaR balance in favor of FcgammaRIIb and completely prevented IgG-triggered TNFalpha production. CONCLUSION: The altered balance of FcgammaR in favor of activating receptors in RA may contribute to increased activation of monocyte/macrophages. A change in the FcgammaR balance toward the inhibitory FcgammaRIIb may offer a novel treatment strategy for preventing the pleiotropic activity of FcgammaR-triggered macrophages.

Adult↗
PubMed1991

Characterization of monocyte chemotactic protein-1 binding to human monocytes.

Monocyte chemotactic protein-1 (MCP-1) stimulates chemotaxis of peripheral blood monocytes. In order to understand the biologic basis of this specific activity, binding studies of 125I-MCP-1 were undertaken. MCP-1 showed saturable binding to monocytes. Scatchard analysis of the monocyte binding data indicate that there are approximately 1,600 high affinity binding sites per monocyte with a Kd = 1.1 nM. Studies with synthetic peptides constructed according to the MCP-1 amino acid sequence indicate that a synthetic peptide, MCP-1[13-35], stimulates monocyte migration and competes with native MCP-1 for binding sites. Inhibition of MCP-1 binding was tested with chemotactic connective tissue proteins. No inhibition of MCP-1 binding was observed with either collagen, elastin-derived peptides or fibronectin. These results identify a single class of unique high affinity MCP-1 binding sites that are likely to recognize a peptide domain on MCP-1 which include the amino acids within the region, 13-35.

Animals↗
PubMed2003

A phylogenetic comparison between acute monocytic leukemia cells and monocytes-macrophages in lower vertebrates.

In humans, monocytes and macrophages (Mphi) play a central role in immune regulation, tissue maintenance and pathogen control. In lower vertebrates, a few studies have been conducted on Mphi like cells. In acute monocytic leukemia monocytic cells, as immature cells restrained in one of the phases of their ontogenesis, would offer the opportunity to rebuild an archaic condition helpful to understand the phylogenesis. Therefore, aim of this work was to characterize in the Rainbow trout (Salmo Gairdneri Richardson) Mphi and compare them with acute leukemia monocytic cells. In the trout, Mphi's morphology is similar to that of mammals. In particular, Mphi possess an irregular embryoshaped nucleus occupying 2/3 of the cell, while the peripheral cytoplasmic profile is irregular with extroflexed plasmalemma and pseudopods. A morphological transition towards Mphi is featured by a wavy hyaline classical membrane and an irregular and extroflexed surface. Some aspects of erythrophagocytosis represented a finding of great interest indicating that the hemocatheretic function could take place directly in circulation. This condition, also observed in human acute monocytic leukemia, suggests that the information to the erythrophagocytosis is restrained under physiological conditions. Non-specific esterases, which are positive in human Mphi smear and Mphi from human lymph node tissue, were also positive in the teleost studied but with a dysomogeneous pattern. Consequently non-specific esterase system is phylogenetically conserved. A lack of immune-reactivity with the anti-CD68 monoclonal antibody (MoAb) on smear and trout tissue sections was observed. On the contrary, strong positivity was detected on human lymph node sections. In trout, the presence of Mphi and circulating Mphi like cells exhibiting an erythrocatheretic function in the circulation would indicate a primordial function that has later been replaced by the liver and the spleen.

Animals↗
PubMed2000

Human THP-1 monocytic leukemic cells induced to undergo monocytic differentiation by bryostatin 1 are refractory to proteasome inhibitor-induced apoptosis.

The ubiquitin-proteasome pathway is the principal mechanism for the degradation of short-lived proteins in eukaryotic cells. We demonstrated that treatment of THP-1 human monocytic leukemia cells with Z-LLL-CHO, a reversible proteasome inhibitor, induced cell death through an apoptotic pathway. Apoptosis in THP-1 cells induced by Z-LLL-CHO involved a cytochrome c-dependent pathway, which included the release of mitochondrial cytochrome c, activation of caspase-9 and -3, and cleavage of Bcl-2 into a shortened 22-kDa fragment. Induction of apoptosis by protease inhibitor also was detected in U937 and TF-1 leukemia cell lines and cells obtained from acute myelogenous leukemia patients but not in normal human blood monocytes. Treatment of human blood monocytes with Z-LLL-CHO did not induce apoptosis or Bcl-2 cleavage in these cells that rarely proliferate. Interestingly, when THP-1 cells were induced to undergo monocytic differentiation by bryostatin 1, a naturally occurring protein kinase C activator, they were no longer susceptible to apoptosis induced by Z-LLL-CHO. Bryostatin 1-induced differentiation of THP-1 cells was associated with growth arrest, acquisition of adherent capacity, and expression of membrane markers characteristic of blood monocytes. Likewise, differentiated THP-1 cells were refractory to Z-LLL-CHO-induced cytochrome c release, caspase activation, and Bcl-2 cleavage. Resistance to Z-LLL-CHO-induced apoptosis in differentiated THP-1 cells was not due to cell cycle arrest. These findings show that the action of proteasome inhibitors is mediated primarily through a cytochrome c-dependent pathway and induces apoptosis in leukemic cells that are not differentiated.

Antineoplastic Agents↗