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PubMed1994

Alterations of regular and mature monocytes are distinct, and dependent of intensity and duration of exercise.

Circulating monocytes comprise functionally distinct regular (CD14bright+) and mature (CD14low+) cells. Cell surface receptors were determined by three colour flow cytometry in 8 healthy control subjects. Compared to regular monocytes, mature monocytes had lower levels of the high affinity Fc gamma receptor 1 (CD64), complement receptor 3 (CD11b), CD45RO and higher levels for HLA-DR, LFA-1 (CD11a/CD18), interleukin-2 receptor (CD25), CD45RA and the Fc gamma receptor 3 (CD16). Both regular and mature monocytes were measured before and up to three hours after four different types of exercise (Ex) in endurance trained athletes (n = 9-16). Immediately after anaerobic exercise of 1 min with a maximal lactate concentration (la max) of 12.3 (SD 1.4) mmol.1-1 and exhaustive exercise of 24 (SD 8) min with a maximal lactate concentration (lamax) of 7.4 (SD 2.6) mmol..-1 mature monocytes increased more than regular monocytes. Exhaustive endurance exercise of 87 (SD 21) min [lamax 3.7 (SD 1.0)] led to a similar increase of regular and mature monocytes. 15-33 min after a 100km run regular monocytes increased significantly, whereas mature monocytes decreased. Up to three hours after the end of all exercises mature monocytes fell below pre-exercise values. In conclusion, duration and intensity of exercise alter distinct maturation stages of monocytes differently. It is probable that the avidity of adhesion molecules like LFA-1 to their endothelial ligands is increased to enable the firm attachment to the endothelium.

Adult↗

PubMed1991

Role of elevated monocyte transforming growth factor beta (TGF beta) production in posttrauma immunosuppression.

We previously reported that increased production of prostaglandin E2 by monocytes is a pivotal mechanism in posttrauma immunopathology. Here we characterize monocyte levels of transforming growth factor beta and examine the effects of elevated transforming growth factor beta on prostaglandin E2 release by patients' monocytes. Trauma patients' and normals' monocyte supernates (+/- stimulation with muramyl dipeptide) were acid treated and assayed for transforming growth factor beta using the mink lung-cell bioassay. Alternatively, human transforming growth factor beta was added to patients' and normals' monocytes and prostaglandin E2 production assayed. Significantly elevated transforming growth factor beta levels (median = 181.7 pmol/10(6) monocytes) were detected in immunosuppressed patients' monocytes but not immunocompetent trauma patients' (median = 32.0 pM) or normals' (median = 20.4 pM) monocytes. Adding transforming growth factor beta to monocytes resulted in a significant elevation of prostaglandin E2 levels. Elevated monocyte transforming growth factor beta levels in trauma patients could be both suppressing T-lymphocyte functions and maintaining elevated monocyte prostaglandin E2 synthesis.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1991

Human lymphokine-activated killer (LAK) cells: III. Effect of L-phenylalanine methyl ester on LAK cell activation from human peripheral blood mononuclear cells: possible protease involvement of monocytes, natural killer cells and LAK cells.

We have shown that depletion of monocytes from human peripheral blood mononuclear cells (PBMC) by L-phenylalanine methyl ester (PheOMe) enhanced lymphokine-activated killer cell (LAK) generation by recombinant interleukin-2 (rIL-2) at high cell density. In this study, we have investigated the mechanism of action of PheOMe on LAK activation by using trypsin, chymotrypsin, tosylphenylalaninechloromethanol (TPCK, a chymotrypsin inhibitor), tosyl-L-lysinechloromethane (TLCK, a trypsin inhibitor), phenylalaninol (PheOH), and benzamidine. PBMC were treated with 1-5 mM PheOMe for 40 min at room temperature in combination with the various agents, washed and assessed for their effects on natural killer (NK) activity against K562 cells and monocyte depletion. The treated cells were then cultured with or without rIL-2 for 3 days. LAK cytotoxicity was assayed against 51Cr-labeled K562 and Raji tumor target cells. TPCK at 10 micrograms/ml partially inhibited depletion of monocytes by PheOMe. TLCK did not prevent depletion of monocytes nor inhibition of NK activity induced by PheOMe. TPCK and TLCK inhibited NK activity by themselves. TPCK but not TLCK inhibited rIL-2 induction of LAK cells. On the other hand, PheOH and benzamidine (analogs of PheOMe) lacked any effect on monocyte depletion but abrogated the inhibitory effect of PheOMe on NK activity. They had no effect on rIL-2 activation of LAK activity enhanced by PheOMe. Trypsin potentiated the inhibitory effect of PheOMe on NK activity and monocyte depletion. Trypsin partially inhibited IL-2 activation of LAK activity enhanced by PheOMe. Chymotrypsin had little effect on NK activity but prevented the inhibitory effect of PheOMe on NK activity. It had little effect on monocyte depletion induced by PheOMe. PheOMe was hydrolysed by monocytes and chymotrypsin to Phe and methanol as determined by HPLC. TPCK inhibited hydrolysis of PheOMe by monocytes. Our data suggest that the effects of PheOMe on monocytes, NK cells and LAK activation involve protease activities of monocytes.

Chymotrypsin↗

PubMed1992

Role of interferon gamma and tumour necrosis factor alpha in monocyte-mediated cytostasis and cytotoxicity against a human histiocytic lymphoma cell line.

In view of cellular adoptive immunotherapy we have studied monocyte-mediated cytostasis and cytotoxicity against U 937 cells, a human histiocytic lymphoma cell line. Highly purified human monocytes and monocyte-derived macrophages were activated with interferon gamma (IFN) or tumour necrosis factor alpha (TNF) to antileukemic immune effector cells. Antileukemic activity of human monocytes was dependent on monocyte differentiation into macrophages and on a dose- and time-dependent activation with IFN or TNF. Maximum cytostasis of 97.0 +/- 0.7% (mean +/- SEM) (conventional [3H]dT uptake assay) and 81.9 +/- 5.3% cytotoxicity (modified MTT assay) of U 937 cells was obtained by monocytes activated with 100 U/ml IFN for at least 24 h at an effector-to-target-cell ratio of 10. U 937 cells premodified with IFN showed an increase in susceptibility to monocyte-mediated cytotoxicity. U 937 cells premodified with TNF were almost resistant to monocyte-mediated cytotoxicity while activated monocytes maintained their cytotoxic potential. These data show that IFN and TNF are potent activators of monocyte-mediated cytotoxicity. Furthermore, IFN and TNF might be involved in the regulation of the susceptibility of leukemic cells to lysis by interactions with monocytes or macrophages.

Cell Death↗

PubMedDate not supplied

Hemodynamic modulation of monocytic cell adherence to vascular endothelium.

Hemodynamic shear stress is hypothesized to contribute to the localization of atherosclerotic plaques to certain arterial sites. Monocyte recruitment to these sites is an early event in artherogenesis. To determine the possible mechanisms by which shear stress modulates monocyte adhesion in vivo, studies of human monocytic cell adherence to endothelium were conducted under different shear conditions in a parallel-plate flow chamber. The number of monocytes capable of developing firm adhesive contacts with endothelium decreased as shear stress-induced drag forces increased over the range of 0.5 to 30 dynes/cm2. The number of adherent monocytic cells at a given shear stress was highly dependent on the activation state of the endothelium. To test the direct effect of shear stress on endothelial cell adhesivity, endothelial cells were presheared for 2 to 6 hr at 2, 10, or 30 dynes/cm2, and monocytic cell adherence was quantified at 1 dyne/cm2. Adherence increased 330% or 370% when endothelial cells were presheared for 2 hr at 2 or 10 dynes/cm2, respectively, as compared to unsheared endothelium. In contrast, when endothelial cells were presheared at 30 dynes/cm2, monocytic cell adherence at 1 dyne/cm2 was not significantly different from unsheared controls. Increased monocytic cell adherence to presheared endothelium was via a vascular cell adhesion molecule 1 (VCAM-1)/alpha(4) beta(1) mechanism, and enzyme-linked immunosorbent assay studies showed that preshearing at 2 dynes/cm2 for 2 hr increased endothelial VCAM-1 expression by 38%. These data demonstrate that low levels of shear stress induce endothelial VCAM-1 expression and increase monocytic cell adherence via a VCAM-1/alpha 4 beta 1 mechanism. Thus, shear stress can modulate monocyte adherence to vascular endothelium through drag forces that affect the establishment and maintenance of adhesive bonds and by directly modulating the expression of endothelial VCAM-1. This dual effect of shear stress produces the most favorable conditions for adhesion at low-shear regions, where drag forces are low and induction of VCAM-1 is likely. The preferential adherence of monocytes to these regions may contribute to the localization of atherosclerotic plaques to low-shear regions of the arterial circulation in vivo.

Antibodies↗

PubMed1984

Interleukin 1 can replace monocytes for the specific human B-cell response to a particulate antigen.

It is shown that the anti-trinitrophenyl (TNP) response of human B cells to trinitrophenyl polyacrylamide beads (TNP-PAA) is monocyte dependent. This response is abolished by extensive adherent cell depletion and restored by the addition of monocytes. The optimal response is obtained with 3% monocytes, higher numbers being suppressive. Supernatants from muramyl dipeptide (MDP)-activated monocytes can restore the response of monocyte-depleted preparations even when cells are cultured at suboptimal concentration. A partially purified preparation of interleukin (IL-1) has a comparable restorative ability. The following arguments suggest that monocytes do not function as antigen-presenting cells for this particulate antigen: (i) antigen-pulsed monocytes induce neither an anti-TNP response nor a specific T-cell proliferative response; (ii) allogeneic monocytes function as well as autologous monocytes to restore the response of nonadherent cells; (iii) HLA-DR-negative cells from the human leukemia cell line K562 can replace monocytes for this response. Monocyte supernatants do not replace T cells for the response of B-enriched lymphocytes, showing that T cells are directly involved in B-cell activation.

Acrylic Resins↗

PubMed1987

Monocyte- and natural killer cell-mediated spontaneous cytotoxicity against human noncultured solid tumor cells.

Unstimulated human peripheral blood mononuclear cells from healthy donors exhibited spontaneous cytotoxicity against noncultured solid tumor targets in a 12- to 24-hr 51Cr release or 111In release assay. Both purified monocytes (greater than 99% monocytes) and natural killer (NK)-enriched lymphocytes exhibited comparable levels of spontaneous cytotoxicity against fresh melanoma tumor targets. This cytotoxicity was observed under endotoxin-free conditions. NK-depleted lymphocytes did not lyse the melanoma targets. Culture supernatants of monocytes incubated with the melanoma tumor cells did not exhibit cytotoxic activity against these targets. Purified monocytes lacked NK activity against the K562 targets in a 4-hr 51Cr release assay. Treatment of the monocytes with anti-Leu 1 1b and anti-Leu7 monoclonal antibodies plus complement did not reduce monocyte-mediated lysis of the melanoma targets, demonstrating that contaminating NK cells, if any, were not responsible for the lysis of noncultured melanoma targets by monocytes. In contrast, Leu 1 1b+ NK cells were responsible for the lysis of the melanoma targets by NK-enriched lymphocytes. The addition of recombinant interferon-gamma (rIFN-gamma), but not lipopolysaccharide, into the 51Cr release assay or pretreatment of monocytes with rIFN-gamma significantly increased their cytotoxicity against noncultured solid tumor cells. Monocytes cultured for 3 days with medium alone lost their cytotoxic activity. The addition of rIFN-gamma from the beginning of these cultures prevented the loss of the cytotoxic activity of monocytes. In summary, both unstimulated monocytes and NK-enriched lymphocytes exhibit comparable levels of spontaneous cytotoxicity against fresh solid tumor targets.

Cells, Cultured↗

PubMed1991

Enumeration of interleukin-1 producing monocytes from human peripheral blood mononuclear leukocytes by agar plating technique.

An agar plating technique was developed for enumeration of IL-1-producing monocytes based on the principle that when IL-1-producing monocytes were cocultured with mouse thymocytes and PHA in semisolid agar medium in a plate, mouse thymocytes proliferated around IL-1-producing monocytes resulting in the clusters or colonies of cells. The IL-1-produced clusters or colonies of cells can be counted under a dissecting microscope. Optimal conditions were established for induction and development of IL-1-producing monocytes. The numbers of IL-1-producing monocytes ranged from 819 to 1930 cells/10(5) monocytes, with mean +/- SEM = 1344 +/- 182 cells/10(5) monocytes; the IL-1 activity ranged from 11.7 to 85.9 U/10(5) monocytes/ml, with mean +/- SEM = 42.8 +/- 11.2 U/10(5) monocytes/ml in seven normal subjects. The IL-1 activity per one monocyte ranged from 12.7 to 86.5 mU, with mean +/- SEM = 33.5 +/- 9.8 mU. The mean numbers of IL-1-producing monocytes and the mean IL-1 levels produced by monocytes from the same normal subjects were highly correlated (r = 0.981). The numbers of IL-1-produced colonies resulting from IL-1-producing monocytes could be completely abolished by incorporation of rabbit anti-human IL-1 in the semisolid agarose but not by rabbit anti-human IL-6 or anti-human TNF-alpha.

Biological Assay↗

PubMed1983

Differential actions of progesterone and cortisol on lymphocyte and monocyte interaction during lymphocyte activation--relevance to immunosuppression in pregnancy.

Progesterone and glucocorticoids share important anti-inflammatory and immunosuppressive properties. Both hormones have potent anti-proliferative effects in MLR, mitogen activation and cytotoxic T-cell generation. We investigated the cellular target of this in vitro anti-proliferative activity by comparing the effects of progesterone and cortisol on lymphocyte-monocyte interaction in concanavalin (Con A) induced human T-cell activation. Three different in vitro systems for assessing monocyte dependent T-cell activation by Con A were used: (1) limiting concentration of monocyte, (2) preincubation of isolated populations of monocytes and T cells with steroids and (3) role of steroid on action of Interleukin-1 (IL-1) activity. Monocytes separated from human peripheral blood leukocytes by flotation gradients and adherence to plastic were cultured at concentrations of 0.5-10% with constant numbers of isolated autologous T cells. Inhibition of Con A activation in cortisol (0.1-10 micrograms/ml) treated cultures was inversely proportional to percent monocytes, whereas in progesterone (2.0-20 micrograms/ml) treated cultures, inhibition was independent of monocyte concentration. Separated monocytes preincubated with progesterone and cultured with fresh T cells supported normal (108 +/- 7% control) levels of activation, but progesterone treated T cells and fresh monocytes responded at about 60% control levels. Similar experiments with cortisol (1 or 10 micrograms/ml) revealed significantly reduced responses when either cell population was preincubated with steroid. IL-1 induced by LPS stimulation of monocytes was blocked in its ability to stimulate Con A induced T cell proliferation with either steroid present during the assay of IL-1. These data provide additional support for local immunosuppression by steroids in the placenta during pregnancy. They suggest that progesterone selectively blocks T cell activation by a direct effect on T cells, whereas cortisol interferes with both monocytes and T cells.

Cells, Cultured↗

PubMed2004

Direct observation and quantitative analysis of spatiotemporal dynamics of individual living monocytes during transendothelial migration.

OBJECTIVE: To visualize and quantitatively analyze spatiotemporal dynamics of individual living monocytes during transendothelial migration (TEM). METHODS AND RESULTS: We developed an in vitro new experimental system using confocal laser scanning microscope with following two improvements: (1) ultra thin collagen gel layer (30-50 microm thick) constructed under human umbilical vein endothelial cell layer for three-dimensional observation with high magnification; (2) appropriate fluorescent labeling of living monocytes and endothelial cells to keep highest cell activity. Individual monocytes behaved quite diversely. Approximately 70% of adhered monocytes directionally crawled to intercellular junction, and started invasion. Time from adhesion to start of invasion was 8.6 +/- 5.4 min (mean +/- S.D., n=61 monocytes). Approximately 80% of such invading monocytes completed TEM, but remaining 20% of once invading monocytes hesitated transmigration, and returned onto the endothelial surface. Time from start to finish of invasion was 6.3 +/- 3.2 min (mean +/- S.D., n=53 monocytes). CONCLUSIONS: Using our collagen gel-based newly-developed system, we visualized and quantitatively analyzed detailed spatiotemporal, three-dimensional dynamics of individual living monocytes during TEM. We revealed that monocytes encountered at least two hurdles, at starting invasion, and leaving endothelium, to achieve complete TEM. Approximately 56% (80% of 70% of adhered monocytes) passed both hurdles.

Cell Movement↗

PubMed2006

Differentiation of monocytes into macrophages induces the upregulation of histamine H1 receptor.

BACKGROUND: Histamine modulates several functions in human monocytes, macrophages, and dendritic cells. However, responses elicited by histamine differ depending on cell type, suggesting variable expression of histamine receptors in the monocyte/macrophage lineage. OBJECTIVE: We sought to examine whether the expression of H(1) receptors was regulated by cell differentiation of human monocytes into macrophages or dendritic cells. METHODS: Expression of H(1) receptor was evaluated by RT-PCR and western blot in monocytes, monocyte-derived macrophages (MDMs), monocyte-derived dendritic cells (DCs) and human lung macrophages (HLMs). RESULTS: Expression of H(1) receptor mRNA and protein was higher in HLMs and DCs than in monocytes. H(1) expression was approximately 15-fold and 4-fold higher in MDMs and HLMs, respectively, as compared with that seen in monocytes. H(1) receptor protein was undetectable in monocytes, whereas it was conspicuous in MDMs. Simultaneous analysis of H(2) and H(1) mRNA expression indicated that the H(2)/H(1) ratio decreased from 202.7 +/- 14.8 in monocytes to 2.2 +/- 0.4 in MDM and 39.5 +/- 5.0 in DCs. Incubation of monocytes with histamine neither affected intracellular Ca(2+) concentrations nor influenced IL-8 production. In contrast, histamine rapidly induced a Ca(2+) signal and stimulated IL-8 production in MDMs. Both effects were inhibited by H(1) blockade with levocetirizine, but not by H(2) blockade with ranitidine. CONCLUSIONS: Differentiation of monocytes into macrophages or dendritic cells is associated with profound changes of histamine receptor expression. Upregulation of H(1) receptors confers on macrophages the capacity of being activated by histamine. CLINICAL IMPLICATIONS: Regulation of H(1) and H(2) receptor expression in the monocyte/macrophage lineage can be relevant to the pathogenesis of allergic inflammation.

Calcium↗

PubMed2005

Monocyte function-associated antigen expression during and after pediatric cardiac surgery.

OBJECTIVE: Systemic inflammatory response syndrome and infectious complications are major causes of morbidity and mortality after cardiopulmonary bypass. Recent work in adult patients suggests that the balance between proinflammatory and anti-inflammatory mediators is important. We hypothesized that the expression of different function-related receptors on circulating monocytes might reflect the net response of the inflammatory reaction. METHODS: We performed a prospective and observational study in a tertiary pediatric cardiac center in a population of children (n = 40) undergoing elective cardiac surgery. Expression of receptors on the surface of monocytes was assessed before, during, and after surgical intervention. RESULTS: Early monocyte activation was demonstrated by changes of the expression of the chemokine receptor CCR2, which was inversely correlated with plasma levels of monocyte chemotactic protein 1 (rho = -0.54, P = .002). High levels of monocyte chemotactic protein 1 were found in children with high expression of the adhesion receptor CD11b/CD18 on circulating monocytes. The intensity of human leukocyte antigen DR expression rapidly decreased in all children after the onset of cardiopulmonary bypass ( P < .001). Low human leukocyte antigen DR expression was correlated with increased plasma levels of interleukin 10 postoperatively. Children who had signs of bacterial pneumonia postoperatively had lower levels of human leukocyte antigen DR expression before surgical intervention (relative risk, 13.3; P = .007). CONCLUSIONS: The expression of monocyte function-related receptors is altered after cardiac surgery. Early activation of monocytes by monocyte chemotactic protein 1 possibly released from the heart is followed by an anti-inflammatory response with suppression of monocyte human leukocyte antigen DR expression. The increased risk of bacterial infection after pediatric cardiac surgery can be anticipated by surveillance of monocyte function before surgical intervention.

CD11 Antigens↗

PubMed2006

Antigens and granularity of blood monocytes in relation to inflammatory markers and lipids in postmenopausal women.

OBJECTIVES: The menopause is associated with an increase of inflammatory markers (C-reactive protein, fibrinogen), cytokines (INFgamma, TNF, etc.) and blood lipoproteins. In vitro, CRP, LDL and fibrinogen can modulate or potentiate interleukines production by monocytes. The aim of this work was to study, the relationships in vivo between hs-CRP, fibrinogen, lipoproteins and the phenotype of circulating monocytes. METHODS: The monocytes phenotype, in postmenopausal women (n=26) without history of cardiovascular disease, was determined, by flow cytometry, measuring granularity and CD14, HLA-DR and CD62-L antigens expression. Blood monocytes were divided in CD14+dim monocytes (low CD14 expression) and CD14+bright monocytes (high CD14 expression). RESULTS: HLA-DR was negatively correlated with hs-CRP and fibrinogen. The relationships between ApoB, LDL/ApoB ratio and CD14 expression was restricted to the CD14+bright monocytes. Blood lipids, i.e. total cholesterol, LDL-c and ApoB were correlated with the granularity of both subsets. CD14+dim monocytes were characterized by a low granularity and CD62-L expression. CONCLUSIONS: Our data show that fibrinogen and hs-CRP are correlated with a reduced antigen-presenting capacity. Expression of CD14 on CD14+bright monocytes is negatively associated to atherogenic LDL. Blood monocytes granularity was positively correlated with serum lipids indicating that monocytes could uptake modified LDL in circulation and not restricted to subendothelial space.

Aged↗

PubMed1994

Monocyte-mediated enhancement of endometrial cell proliferation in women with endometriosis.

OBJECTIVE: To investigate the capacity of monocytes from women with endometriosis to influence endometrial cell proliferation. DESIGN: Uterine endometrial cells were cultured in the presence and absence of autologous blood monocytes for 72 hours before assessment of endometrial cell proliferation by thymidine incorporation. SETTING: Patients were tested at initial presentation for evaluation of infertility and/or endometriosis. PATIENTS, PARTICIPANTS: Fertile controls, n = 17; infertile controls, n = 9; untreated endometriosis, n = 29. INTERVENTIONS: None. RESULTS: Endometrial cell proliferation was enhanced significantly by blood monocytes in patients with endometriosis but was suppressed significantly by blood monocytes in fertile controls. Endometrial cell proliferation was not affected significantly by blood monocytes in infertile controls analyzed as a group, but a subset of infertile patients also showed enhancement of endometrial cell proliferation by blood monocytes. CONCLUSIONS: Blood monocytes from patients with endometriosis and a subset of patients with unexplained infertility enhance autologous endometrial cell proliferation, whereas blood monocytes from fertile patients suppress endometrial cell proliferation. The capacity of monocytes to enhance endometrial cell proliferation appears to require both monocyte-derived factors that stimulate endometrial cell proliferation and endometrial cells capable of responding to those stimulatory factors. If either of these factors is absent, monocytes either suppress or have no effect on endometrial cell proliferation.

Adult↗

PubMed1997

Monocyte tissue factor expression, cell activation, and thrombin formation during cardiopulmonary bypass: a clinical study.

OBJECTIVES: Cardiopulmonary bypass is associated with extensive thrombin generation and cell activation. Our main hypothesis in this study was that the expression of tissue factor on circulating monocytes contributes to the formation of thrombin. METHODS: Markers of activation of the coagulation cascade and cell activation were measured in 26 patients undergoing elective heart operations randomized to the use of heparin-coated (Duraflo II, n = 13) or standard cardiopulmonary bypass circuits (n = 13). RESULTS: Thrombin generation, measured as the thrombin-antithrombin complex, increased considerably during cardiopulmonary bypass with peak levels 3 hours afterward and with remaining elevation 20 hours later. Despite increased monocyte and granulocyte activation and increased levels of monocyte chemotactic protein-1, which upregulates monocyte tissue factor expression in vitro, monocyte tissue factor expression was not increased at the end of cardiopulmonary bypass. Furthermore, at this time the monocytes were less sensitive to in vitro stimulation by endotoxin. These results might be explained by simultaneous enhanced levels of interleukin-10, which effectively downregulates monocyte tissue factor expression in vitro. Twenty hours after cardiopulmonary bypass was discontinued, the tissue factor expression on freshly isolated monocytes and on monocytes stimulated by endotoxin was significantly increased compared with preoperative levels. At this time increased activation markers of granulocytes, monocytes, and lymphocytes were also recorded. None of the measured parameters was found to be different between the groups. CONCLUSIONS: The tissue factor expression on circulating monocytes is upregulated the day after heart operations. The clinical relevance and the regulatory mechanism behind the enhanced expression, however, are not fully elucidated.

Aged↗

PubMed1999

Phenotypic and functional characteristics of circulating monocytes of elderly persons.

Aging is associated with impairment of immune functions. Age-dependent alterations in T-cells are well known. Although the pivotal role of monocytes in immune regulation by their production of proinflammatory and inhibitory cytokines is acknowledged, limited information is available on monocyte changes in aging. The present study focused on phenotypic changes in circulating monocytes in elderly subjects and in the level of cytokines they produce. The results demonstrated a significant expansion of CD14dim/CD16bright circulating monocytes in elderly. In contrast, the majority of circulating monocytes of healthy young individuals were CD14bright/CD16dim. The CD14dim/CD16bright monocytes are considered to have phenotypic evidence for activation. Furthermore, significant increases of constitutive production of monocytic cytokines including interleukin (IL)-1beta. IL-1 receptor antagonist, and IL-6 by nonstimulated monocytes from elderly was also indicative of activation. This was also observed when monocytes from elderly were cultured with autologous lymphocytes. However, after stimulation, significantly lowered IL-1beta production was observed and IL-6 and IL-10 tended to be higher in the elderly. Collectively, these results indicate that monocytes of aged individuals, in contrast to a younger population exhibit in vivo activation as well as imbalanced production of cytokines. Such age-related alterations in monocytes may contribute to impaired immune competence of aging.

Adult↗

PubMed2002

Monocyte activation in alcoholic liver disease.

Activated monocytes and macrophages have been postulated to play an important role in the pathogenesis of alcoholic liver disease (ALD). Monocyte activation can be documented by measurement of neopterin, adhesion cell molecules, and certain proinflammatory cytokines and chemokines. We first became interested in the role of monocytes and monocyte-derived cytokines in ALD in relation to altered zinc metabolism that occurs regularly in ALD. Patients with ALD have hypozincemia, which responds poorly to oral zinc supplementation. We have shown that in ALD monocytes make a low-molecular-weight substance that, when injected into rabbits, causes prominent hypozincemia. Subsequently, multiple cytokines [especially tumor necrosis factor (TNF) and interleukin (IL)-8] have been shown to be overproduced by monocytes in ALD. We initially showed that monocytes in ALD spontaneously produce TNF and overproduce TNF in response to a lipopolysaccharide (LPS) stimulus, and this could be attenuated by antioxidants in vitro and in vivo. Alterations in the endotoxin-binding protein LPS-binding protein, in CD14, and in the endotoxin receptor Toll-like receptor 4 all may play roles in enhanced proinflammatory cytokine signaling in ALD. Moreover, several groups have documented increased TNF receptor density in monocytes in ALD. Inadequate negative regulation of TNF occurs at multiple levels in ALD. This includes decreased monocyte production of the important antiinflammatory cytokine IL-10 and blunted response to the antiinflammatory properties of adenosine. Finally, generation of reactive oxygen species (which occurs during alcohol metabolism) and products of lipid peroxidation induce production of cytokines, such as TNF and IL-8. In conclusion, there are multiple overlapping potential mechanisms for enhanced proinflammatory cytokine production by monocytes in ALD. We postulate that activation of monocytes and macrophages with subsequent proinflammatory cytokine production plays an important role in certain metabolic complications of ALD and is a component of the liver injury of ALD.

Animals↗

PubMed2003

Allergen-dependent CD14 modulation and apoptosis in monocytes from allergic patients.

BACKGROUND: CD14 is a most important monocyte surface molecule. Recently, it has been reported that there is an important relationship between CD14 and immunoglobulin E, and that regulation of CD14 expression is an effector mechanism mediating apoptosis of monocytes. OBJECTIVE: The present study was designed to determine whether specific allergens were able to modulate CD14 expression and apoptosis by monocytes from allergic patients or whether specific immunotherapy (IT) might affect these processes. METHODS: One group of adult allergic asthmatic patients had received IT for the previous 3 years. Another similar group was not treated with IT. We challenged peripheral blood monocytes from both groups of asthmatic patients in vitro with the specific allergen that produced clinical symptoms in asthmatic patients. The cells were also challenged with allergen to which the patients were not sensitive. Monocytes from normal subjects were also challenged with allergens. Expression of CD14 on the monocyte surface was analyzed by flow cytometry, and soluble CD14 (sCD14) in culture supernatant by enzyme-linked immunosorbent assay. The three groups of subjects were challenged with allergens, and apoptosis was analyzed by flow cytometry. RESULTS: When monocytes from non-IT-treated asthmatic patients were cultivated with the allergens to which the patients were sensitive, a significant up-regulation on the monocyte surface was observed compared with results from the healthy group (P < 0.003) and from the IT asthmatic group (P < 0.003). A significantly higher sCD14 level was observed in the culture supernatant of the monocytes from the IT asthmatic group were observed compared with those from the healthy group (P < 0.001) and those from the non-IT asthmatic group (P < 0.001). A significantly higher apoptosis level was observed in monocytes from the IT asthmatic group compared with those from the healthy group (P < 0.001) and those from the non-IT asthmatic group (<0.001). CONCLUSIONS: We present evidence that the expression of CD14 on the surface of monocytes and the apoptosis of the same cells can be modulated by an allergen-dependent mechanism. These processes can be affected by IT.

Adult↗