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 1,009 records · Page 56Linked to original sources
PubMed1999

MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions.

Monocytes contribute to the development of atherosclerotic lesions in mouse models. The chemoattractant proteins (chemokines), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), are found in human atheroma, and mice lacking receptors for these chemokines are less susceptible to atherosclerosis and have fewer monocytes in vascular lesions. Although MCP-1 has a powerful effect on monocytes, IL-8 is thought to act predominantly on neutrophils and it is unclear how it could recruit monocytes. Here we investigate the ability of chemokines to control the interaction of monocytes under flow conditions with vascular endothelium that has been transduced to express specific leukocyte-adherence receptors. We find that MCP-1 and IL-8 can each rapidly cause rolling monocytes to adhere firmly onto monolayers expressing E-selectin, whereas related chemokines do not. These effects do not correlate with either the induction of a calcium transient or chemotaxis. We conclude that chemokines are important modulators of monocyte-endothelial interactions under flow conditions. Moreover, our finding that IL-8 is a powerful trigger for firm adhesion of monocytes to vascular endothelium reveals an unexpected role for this chemokine in monocyte recruitment.

Cell Adhesion↗
PubMed1992

Chemoattractants provoke monocyte adhesion to human mesangial cells and mesangial cell injury.

Infiltration of glomerular mesangium by monocytes/macrophages is a prominent pathologic finding in many forms of glomerulonephritis (GN). While the mechanism(s) by which infiltration occurs is incompletely understood, monocyte adhesion to glomerular endothelial cells, provoked by inflammatory mediators, appears to be an important early step. In the present study, we assessed the influence of chemotactic peptides (C5a) and lipids (LTB4 and PAF) on adhesion of human monocytes and mesangial cells, to determine if mesangial cells (glomerular pericytes with smooth muscle properties) represent potential targets for adhesion of chemoattractant-activated monocytes following their diapedesis from the intravascular space. C5a and LTB4 provoked rapid (onset less than 1 min) monocyte-mesangial cell adhesion at nanomolar concentrations via actions with monocytes, while PAF was less potent in this regard. Monoclonal antibodies (mAb) were used to define the monocyte and mesangial cell adhesion molecules involved in these interactions. C5a- and LTB4-induced monocyte adhesion was inhibited (approximately 54%) by mAb against the common beta CD18 subunit of CD11/CD18 leukocyte integrins, while mAb against monocyte L-selectin was without effect. MAb against unique CD11 subunits were used to determine the relative contributions of different CD11/CD18 integrins. In this regard, adhesion was inhibited by mAb against CD11b (approximately 41%), and CD11c (approximately 23%), but not CD11a. MAb against mesangial cell ICAM-1 afforded approximately 27% reduction in adhesion, while mAb against VCAM-1, E-selectin, and P-selectin were without effect. GM-CSF, a cytokine generated by monocytes and mesangial cells, also provoked CD11/CD18-dependent adhesion, and primed monocytes to the actions of chemoattractants.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1999

Coexpression of tissue factor and tissue factor pathway inhibitor by human monocytes purified by leukapheresis and elutriation. Response of nonadherent cells to lipopolysaccharide.

BACKGROUND: Counterflow centrifugal elutriation is the method of choice for obtaining a large quantity of highly purified monocytes. In spite of the fact that this technique has been used for many years to isolate monocytes for cellular immunotherapy, it is not known whether the process of elutriation can stimulate tissue factor (TF) expression and therefore trigger coagulation in patients receiving these cell preparations. The aim of the present study is thus to identify TF and TF pathway inhibitor (TFPI) in elutriated monocytes and to evaluate their ability to trigger thrombin generation. STUDY DESIGN AND METHODS: Human monocytes are separated by leukapheresis and elutriation in sterile, endotoxin-free conditions. TF and TFPI mRNA is detected by reverse transcription-polymerase chain reaction. TF and TFPI are measured by enzyme-linked immunosorbent assay in cell lysates. TF antigen expression on cell surface is evidenced by direct-flow cytometry. Two functional tests (a chronometric test and an amidolytic assay) assess the capacity of monocytes to trigger thrombin generation. The response to lipopolysaccharide (LPS) is evaluated with each technique. Monocytic cell line THP-1 is used as a positive control. RESULTS: Elutriated monocytes coexpress TF mRNA and TFPI mRNA. The expression of TF mRNA is dramatically increased by LPS activation. This is correlated with a 100-fold increase in the amount of TF antigen in monocyte lysates. Flow immunocytometry confirms the expression of TF antigen on cell membrane in response to LPS stimulation, whereas TFPI mRNA is slightly increased after LPS stimulation. The amount of TFPI antigen in cell lysates is small when compared to that in plasma. Elutriated monocytes have a strong potential to trigger thrombin generation in response to LPS. CONCLUSION: In spite of the coexpression of TF mRNA and TFPI mRNA, elutriated monocytes are capable of supporting prothrombinase activity. This should be taken into account in the evaluation of the safety of adoptive cellular immunotherapy.

Antigens↗
PubMed2005

Differentiation of in vitro-modified human peripheral blood monocytes into hepatocyte-like and pancreatic islet-like cells.

BACKGROUND & AIMS: Adult stem cells provide a promising alternative for the treatment of diabetes mellitus and end-stage liver diseases. We evaluated the differentiation potential of human peripheral blood monocytes into hepatocyte-like and pancreatic islet-like cells. METHODS: Monocytes were treated with macrophage colony-stimulating factor and interleukin 3 for 6 days, followed by incubation with hepatocyte and pancreatic islet-specific differentiation media. Cells were characterized by flow cytometry, gene-expression analysis, metabolic assays, and transplantation for their state of differentiation and tissue-specific functions. RESULTS: In response to macrophage colony-stimulating factor and interleukin 3, monocytes resumed cell division in a CD115-dependent fashion, which was associated with a down-regulation of the PRDM1 and ICSBP genes. These programmable cells of monocytic origin were capable of differentiating into neohepatocytes, which closely resemble primary human hepatocytes with respect to morphology, expression of hepatocyte markers, and specific metabolic functions. After transplantation into the liver of severe combined immunodeficiency disease/nonobese diabetic mice, neohepatocytes integrated well into the liver tissue and showed a morphology and albumin expression similar to that of primary human hepatocytes transplanted under identical conditions. Programmable cells of monocytic origin-derived pancreatic neoislets expressed beta cell-specific transcription factors, secreted insulin and C peptide in a glucose-dependent manner, and normalized blood glucose levels when xenotransplanted into immunocompetent, streptozotocin-treated diabetic mice. Programmable cells of monocytic origin retained monocytic characteristics, notably CD14 expression, a monocyte-specific methylation pattern of the CD115 gene, and expression of the transcription factor PU.1. CONCLUSIONS: The ability to reprogram, expand, and differentiate peripheral blood monocytes in large quantities opens the real possibility of the clinical application of programmable cells of monocytic origin in tissue repair and organ regeneration.

Albumins↗
PubMed1994

P-selectin induces the expression of tissue factor on monocytes.

P-selectin on activated platelets and stimulated endothelial cells mediates cell adhesion with monocytes and neutrophils. Since activated platelets induce tissue factor on mononuclear leukocytes, we examined the effect of P-selectin on the expression of tissue factor activity in monocytes. Purified P-selectin stimulated tissue factor expression on mononuclear leukocytes in a dose-dependent manner. Chinese hamster ovary (CHO) cells expressing P-selectin stimulated tissue factor procoagulant activity in purified monocytes, whereas untransfected CHO cells and CHO cells expressing E-selectin did not. Anti-P-selectin antibodies inhibited the effects of purified P-selectin and CHO cells expressing P-selectin on monocytes. Incubation of CHO cells expressing P-selectin with monocytes leads to the development of tissue factor mRNA in monocytes and to the expression of tissue factor antigen on the monocyte surface. These results indicate that P-selectin upregulates the expression of tissue factor on monocytes as well as mediates the binding of platelets and endothelial cells with monocytes and neutrophils. The binding of P-selectin to monocytes in the area of vascular injury may be a component of a mechanism that initiates thrombosis.

Cell Adhesion Molecules↗
PubMed1995

Human coagulation factor V is activated to the functional cofactor by elastase and cathepsin G expressed at the monocyte surface.

The ability of intact peripheral blood monocytes to modulate factor V procoagulant activity was studied using electrophoretic and autoradiographic techniques coupled to functional assessment of cofactor activity. Incubation of plasma concentrations of factor V with monocytes (5 x 10(6)/ml) resulted in the time-dependent cleavage of the 330-kDa protein. Activation occurred via several high molecular mass intermediates (> or = 200 kDa) to yield peptides of 150, 140, 120, 94, 91, 82, and 80 kDa, which paralleled the expression of cofactor activity. The cleavage pattern observed differed from that obtained with either thrombin or factor Xa as an activator. The incubation time required to achieve full cofactor activity was dependent on the monocyte donor and ranged from 10 min to 1 h and was consistently slightly lower than that obtained with thrombin-activated factor Va. Cofactor activity was not diminished by additional incubation. The cofactor activity generated bound to the monocyte such that a competent prothrombinase complex was formed at the monocyte membrane surface. Furthermore, within 5 min of factor V addition to monocytes, near maximal cofactor activity (approximately 70%) was bound and expressed on the monocyte membrane. The proteolytic activity toward factor V was associated primarily with the monocyte membrane, as little proteolytic activity was released into the cell-free supernatant. Proteolytic activity was inhibited by diisopropyl fluorophosphate and phenylmethanesulfonyl fluoride. However, the inhibitor profile obtained with alpha 1-antiproteinase inhibitor, alpha 1-antichymotrypsin, and alpha 2-macroglobulin suggested membrane-bound forms of elastase and cathepsin G were mediating, in large part, the proteolysis observed. These data were confirmed using purified preparations of both proteases and a specific anti-human leukocyte elastase antibody. Thus, expression of these proteases at the monocyte surface may contribute to thrombin generation at extravascular tissue sites by catalyzing the activation of the essential cofactor, factor Va, which binds to the monocyte surface and supports the factor Xa-catalyzed activation of prothrombin.

Cathepsin G↗
PubMed2004

Platelet-derived microvesicles transfer tissue factor to monocytes but not to neutrophils.

Activated platelets are known to adhere to both blood monocytes and neutrophils, and this adhesion is mainly mediated by the surface exposure of the platelet granule protein CD62P. Platelets as well as platelet-derived microvesicles (PMV) have also been shown to contain and to transfer tissue factor (TF), the most important initiator of intravascular thrombin and fibrin formation, to monocytes. However, the role of neutrophils for gathering platelet-derived TF is controversial. Here we studied the interaction of PMV with monocytes and neutrophils using a whole blood system. Platelet-rich plasma (PRP) obtained from citrated human blood was incubated with collagen (5 microg/ml, 15 min) and the platelets were removed by centrifugation (5 min at 5000 x g). After incubating the PMV-containing plasma for further 30 min with a sediment of red and white bloods cells that had been obtained after PRP preparation, monocytes and neutrophils were analysed by flow cytometry for the surface exposure of the platelet-specific antigen CD42a and TF. Compared to a control with non-activated PRP, there was a significant increase in the number of both CD42a-positive monocytes and neutrophils. In contrast, there was no change in the number of TF-positive neutrophils, but a more than 2-fold increase in the number of TF-positive monocytes. The changes in CD42a on monocytes and neutrophils as well as the changes in TF on monocytes could be significantly reduced by an anti-CD62P antibody or by removal of PMV from the plasma samples. The data indicate that the transfer of TF to monocytes is not simply an CD62P-mediated adhesion of platelets or PMV to monocytes, but may involve other not yet identified mechanisms.

Biological Transport↗
PubMed1993

Differential effect of human and murine polyclonal and monoclonal antisera on TNF-alpha production by human monocytes.

The capacity of human and murine polyclonal and monoclonal antibodies to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) release from human monocytes was investigated. Human pooled immunoglobulin G (IVIG), human IgM monoclonal antibody (HA-1A) directed against the lipid A moiety of LPS, and murine IgG monoclonal antibody (MT-1F) raised in mice against antibiotic-treated Escherichia coli O6:K- were either added simultaneously with LPS to monocytes or preincubated for 1 h at 37 degrees C before being added to monocytes. TNF-alpha content in the monocyte supernatants was then tested. Simultaneous addition of increasing concentrations of IVIG (from 0.3 to 2.5 mg/ml) and 10 micrograms/ml of LPS to monocytes induced an enhanced release of TNF-alpha by monocytes in a dose dependent fashion. Preincubation of IVIG with LPS abolished the additive effect, but did not inhibit LPS-induced TNF-alpha release by monocytes. The simultaneous addition of LPS and HA-1A to monocytes had no additive effect nor did it inhibit TNF-alpha release. On the other hand, inhibition of TNF-alpha release was observed when HA-1A was preincubated with LPS before being added to monocytes. In all instances MT-1F inhibited TNF-alpha release when the monocytes were stimulated with smooth type LPS, but not with LPS isolated from rough mutants.

Animals↗
PubMed1975

Inhibition of multiplication of Toxoplasma gondii by human monocytes exposed to T-lymphocyte products.

The multiplication of Toxoplasma gondii was quantitated in human monocytes in vitro by phase-contrast microscopy. Toxoplasma multiplication was identical in monocytes from subjects byt was significantly inhibited in cells from both sources if the monocytes were preincubated with immune lymphocytes and toxoplasma monocytes were preincubated with immune lymphocytes and toxoplasma antigen. Supernates prepared from toxoplasma-immune lymphocytes incubated with toxoplasma antigen were also effective in inducing in monocytes the capacity to inhibit toxoplasma multiplication. Supernative acitivty was evident after lymphocytes and antigen were incubated for as little as 15 min. The instruction of monocytes was also repid and reversible. Monocytes were fully induced to inhibit toxoplasma multiplication after a 2 h exposure to an active supernate, but they lost their inhibitory capacity on culture in vitro for 48 h in the absece of immune cells or their products. The lymphocytes particupating in the monocyte induction were identified as t cells. The in vitro stimulation of monocytes appeared to exhibit some specificity, since no inhibition of toxopreotein derivative and lymphocytes from tuberculin-positive subjects, concanavalin a-stimulated lymphocytes, or their supermates. Supernates which induced monocytes to inhibit toxoplasma multiplication did not influence parasite growth in HeLa cells.

Adult↗
PubMed1981

Receptors for cold-insoluble globulin (plasma fibronectin) on human monocytes.

This investigation focused on the role played by cold-insoluble globulin (CIg, plasma fibronectin) in monocyte function. Surface-bound CIg mediated a concentration-dependent of human blood monocytes to gelatin-coated surfaces. CIg also mediated the binding of gelatin-coated particles such as latex beads or tanned erythrocytes to surface-bound human monocytes. However, CIg did not mediate particle ingestion. Subfractionated CIg that was highly enriched in monomeric forms (zone II CIg, mol wt 190,000-235,000) was less effective than were fractions enriched in dimeric forms (zone I CIg, mol wt 450,000) in promoting monocyte attachment. Binding of CIg to a gelatin or plastic surface occurred in the absence of divalent cations, but monocyte attachment to CIg-coated surfaces required divalent cations, Mg++ being much more effective than Ca++. Cation-dependent cell attachment was reversible in that bound cells could be released by treatment with EDTA. Serum-mediated binding of monocytes to gelatin-coated plastic dishes was a result of its content of CIg because the binding activity was abolished by removal of CIg from serum, and could be restored by readdition of purified CIg. Treatment of monocytes with trypsin abolished subsequent cell attachment to CIg-gelatin surfaces or particles. Expression of certain other known monocyte membrane receptors (Fc and C3b) was markedly enhanced as a result of CIg-monocyte interaction. These several observations indicate that monocytes bear membrane receptors (termed receptor cold-insoluble globulin) for surface-bound CIg.

Cations, Divalent↗
PubMed1985

A fast-acting elastase inhibitor in human monocytes.

A proteinase inhibitor active against neutrophil and pancreatic elastase was detected in extracts of cultured human monocytes and the human monocyte-like cell line U937. This component forms a covalent complex with the active site of elastase; the complex is stable in boiling sodium dodecyl sulfate solution, and is susceptible to nucleophilic cleavage. The activity of the elastase inhibitor is not detected in extracts of freshly isolated monocytes, but becomes detectable when the monocytes are allowed to mature in culture, with maximum levels occurring at 5-7 d. The monocyte inhibitor is fast-acting; its reaction with 125I-labeled elastase is complete in less than 1 min at 37 degrees C. Analysis by electrophoresis and studies using a heteroantiserum to alpha 1-proteinase inhibitor demonstrated that the elastase inhibitor of monocytes/U937 cells is not identical to alpha 1-proteinase inhibitor, the major elastase inhibitor of blood plasma. The extent of conversion of 125I-elastase to the 125I-elastase-inhibitor complex is proportional to the amount of U937 extract or cultured monocyte extract, indicating that this reaction can serve to quantify the elastase inhibitor. The elastase inhibitor is an abundant component in mature monocytes, with greater than or equal to 1.5 X 10(6) molecules/cell (greater than or equal to 12 micrograms per 10(8) cells, greater than 0.1% of total cell protein). Its mol wt is estimated at 50,000. Thus, the monocyte inhibitor should be classified as a putative regulator of neutrophil (and monocyte) elastase activity at inflammatory sites. This designation is based on the properties of the molecule, including its high concentration in maturing monocytes, its affinity for elastase, and its fast reaction with this enzyme.

Blood Proteins↗
PubMed1988

The selective binding and transmigration of monocytes through the junctional complexes of human endothelium.

Human monocytes show a high affinity for vascular endothelium both in vitro and in vivo. To explore monocyte-endothelial interaction in greater detail, we have developed a new in vitro model for growth of human endothelial cells (EC). Human umbilical vein EC (HUVEC) cultured upon collagen gels form confluent monolayers of EC that bind silver at their intercellular border similar to cells in situ. Intercellular junctional structures, both adherens and tight junctions, were identified. In contrast, HUVEC grown on plastic surfaces did not stain with silver. The silver-staining characteristic of EC-collagen monolayers was reversible and related to their in vitro maturation and senescence. Silver staining of EC borders provided a grid by which the location of monocyte binding to the luminal surface of individual EC could be assessed. Using this technique, we found that monocytes preferentially bound to the margins of EC, in approximation to the silver-staining junctions. These results suggest that EC determinants recognized by monocytes occur in a unique topographical distribution on the apical face of EC. After binding, monocytes migrated through the EC monolayers at high basal rates. The lack of penetration of collagen gels in the absence of an EC monolayer suggested the generation of EC-specific chemotactic signal(s). Monocytes were observed to pass between EC without evidence of disruption of the monolayer. Silver stain remained present during all phases of migration, and under transmission electron microscopy, junctional complexes were found proximal to monocytes that had just completed their passage through the monolayer. After orientation to the basal surface of the EC monolayer, monocytes migrated randomly into the underlying collagen gel. Monocyte adherence, penetration, migration, and long term survival can be studied under these conditions.

Cell Adhesion↗
PubMed1993

Heat-shock proteins protect cells from monocyte cytotoxicity: possible mechanism of self-protection.

We have previously shown that major heat-shock protein (hsp 70) protects WEHI-S tumor cells from cytotoxicity mediated by tumor necrosis factor alpha (TNF-alpha) and TNF-beta. In the present study, the effect of altered expression of hsp70 and low molecular weight heat-shock protein, hsp27, on tumor cell sensitivity to monocytes and lymphokine-activated killer (LAK) cells was studied. Constitutive and stable expression of transfected human hsp70 rendered cells almost completely resistant to monocytes. Conversely, inhibition of endogenous hsp70 by expression of antisense hsp70 RNA enhanced the sensitivity of cells to monocyte-mediated killing. Surprisingly, overexpression of human hsp27, which does not protect WEHI-S cells from TNF killing, conferred partial resistance to monocytes. Only approximately 60% of monocyte-mediated killing of WEHI-S cells could be blocked by neutralizing TNF-alpha antibody or immunoglobulin G-TNF receptor chimeric protein, suggesting the presence of both TNF-dependent and TNF-independent lytic mechanisms. As free radicals have been suggested to be mediators of monocyte cytotoxicity, we tested the sensitivity of transfected cells to oxidative stress. Overexpression of either hsp70 or hsp27 rendered cells partially resistant to hydrogen peroxide. No significant changes in the susceptibility of cell lines overexpressing hsp70 or hsp27 to cytotoxicity mediated by LAK cells were observed. Interestingly, monocytes but not LAK cells contained detectable levels of hsp27 and hsp70 in nonstressed conditions. Taken together, these data indicate that hsp70 protects tumor cells from TNF-mediated monocyte cytotoxicity and that both hsp27 and hsp70 confer resistance to TNF-independent, probably free radical-mediated lysis by monocytes. Moreover, hsp27 and hsp70 may provide monocytes with a protective mechanism against their own toxicity.

Animals↗
PubMed2006

Immature monocytes acquire antigens from other cells in the bone marrow and present them to T cells after maturing in the periphery.

Monocytes are circulating precursors for tissue macrophages and dendritic cells (DCs) but are not recognized to directly participate in antigen presentation. We developed techniques to label mouse monocyte subsets with particulate tracers in vivo. Gr-1lo but not Gr-1hi monocytes were stably labeled by intravenous injection of 0.5-microm microspheres. Gr-1hi monocytes could be labeled when the microspheres were injected after systemic depletion of blood monocytes and spleen macrophages. In this condition, the phagocytic tracer was transferred to immature bone marrow monocytes by neutrophils and B cells that first carried the particles to the bone marrow. Moreover, antigens from B cells or proteins conjugated to the tracer particles were processed for presentation by monocytes and could induce T cell responses in the periphery. Cell-associated antigen taken up by bone marrow monocytes was retained intracellularly for presentation of the antigen days later when monocyte-derived DCs migrated to lymph nodes or in vitro after differentiation with granulocyte/macrophage colony-stimulating factor. These data reveal that immature monocytes unexpectedly sample antigen from the bone marrow environment and that they can present these antigens after they leave the bone marrow.

Animals↗
PubMedDate not supplied

Mechanisms of monocyte recruitment in vascular repair after injury.

The inflammatory response to acute vessel wall injury has been increasingly recognized to play a decisive role in neointima formation. In particular, the exuberant infiltration with monocytes aggravates neointimal growth and can thereby promote restenosis. The adhesion of circulating monocytes to the site of mechanical injury represents the key event in monocyte recruitment, and this review highlights recent insights into the molecular mechanisms of monocyte adhesion throughout the course of neointimal growth. An acute and a chronic phase of monocyte recruitment after vascular injury can be discerned. The adhesion of platelets to the denuded subendothelial matrix is the hallmark of the acute phase providing an adhesive substrate for monocytes, whereas chronic monocyte recruitment is regulated by the interaction with neointimal smooth muscle cells and recovering endothelial cells. Clearly, the mechanisms of monocyte rolling and adhesion differ considerably between these diverse substrates. This review is particularly focused on the contribution of chemokines and adhesion molecules to monocyte recruitment to injured vessels according to the different stages of neointimal growth, and on closely related functions of the chemokine-like molecule macrophage migration inhibitory factor. Understanding the complex molecular interactions of the injured vessel wall with circulating monocytes may enable therapeutic targeting to prevent the development of restenosis.

Animals↗
PubMed2004

Distinct responses of monocytes to Toll-like receptor ligands and inflammatory cytokines.

In this study we compared the activation of monocytes by different bacterial products via Toll-like receptors (TLR), and by different proinflammatory mediators. In response to TLR-2, -4 and -5 engagement, approximately 50% of monocytes produced TNF-alpha, compared to only 5% after induction with IFN-gamma or GM-CSF. Furthermore, a small proportion of monocytes produced IL-10 after stimulation via TLR, but not after stimulation with cytokines. Both TLR-ligands and inflammatory cytokines induced the expression of CD25, CD69, CD80 and, surprisingly, also of CD83, commonly regarded as an activation marker for mature dendritic cells (DC). Conversely, TLR-ligands downregulated CD38, CD86 and ICOS-L. Importantly, signaling lymphocytic activation molecule (SLAM; CD150) was identified as a monocyte activation marker that could be induced ex novo via TLR-2, -4 and -5, but not by single stimulation with monocyte activators like IL-1, TNF-alpha, IFN-beta, IFN-gamma, GM-CSF or CD40-L. SLAM expression was transient and required mitogen activated protein kinase (MAPK) p38, but not ERK or JNK, and was surprisingly independent of NF-kappaB. SLAM+ monocytes, which are absent in blood, were detected in spleen and tonsils, where they could be localized to T-cell areas and germinal centers. Together, by comparing the response of monocytes to TLR-ligands and inflammatory cytokines, we have identified a monocyte activation marker, SLAM, which differs in its inducibility from other monocyte activation markers. SLAM+ monocytes and macrophages were identified for the first time in vivo. Their presence might be a sign of innate immune activation.

Antigens, CD↗
PubMed2005

HIV-1 induces IL-10 production in human monocytes via a CD4-independent pathway.

In HIV-infected patients, increased levels of IL-10, mainly produced by virally infected monocytes, were reported to be associated with impaired cell-mediated immune responses. In this study, we investigated how HIV-1 induces IL-10 production in human monocytes. We found that CD14(+) monocytes infected by either HIV-1(213) (X4) or HIV-1(BaL) (R5) produced IL-10, IL-6, tumor necrosis factor-alpha (TNF-alpha), and to a lesser extent, IFN-gamma. However, the capacity of HIV-1 to induce these cytokines was not dependent on virus replication since UV-inactivated HIV-1 induced similar levels of these cytokines. In addition, soluble HIV-1 gp160 could induce CD14(+) monocytes to produce IL-10 but at lower levels. Cross-linking CD4 molecules (XLCD4) with anti-CD4 mAbs and goat anti-mouse IgG (GAM) resulted in high levels of IL-6, TNF-alpha and IFN-gamma but no IL-10 production by CD14(+) monocytes. Interestingly, neither anti-CD4 mAbs nor recombinant soluble CD4 (sCD4) receptor could block IL-10 secretion induced by HIV-1(213), HIV-1(BaL) or HIV-1 gp160 in CD14(+) monocytes, whereas anti-CD4 mAb or sCD4 almost completely blocked the secretion of the other cytokines. Furthermore, HIV-1(213) could induce IL-10 mRNA expression in CD14(+) monocytes while XLCD4 by anti-CD4 mAb and GAM failed to do so. As with IL-10 protein levels, HIV-1(213)-induced IL-10 mRNA expression in CD14(+) monocytes could not be inhibited by anti-CD4 mAb or sCD4. Taken together, HIV-1 binding to CD14(+) monocytes can induce CD4-independent IL-10 production at both mRNA and protein levels. This finding suggests that HIV induces the immunosuppressive IL-10 production in monocytes and is not dependent on CD4 molecules and that interference with HIV entry through CD4 molecules may have no impact on counteracting the effects of IL-10 during HIV infection.

Antibodies↗
PubMed1987

Characterization of formylpeptide chemoattractant binding on neutrophils and monocytes from patients with head and neck cancer.

Monocytes from patients with head and neck tumors display a marked chemotactic deficiency in response to formylpeptide chemoattractants. Normal leukocytes possess receptors known to bind to chemotactic formylpeptides such as the hexapeptide N-formyl-nor-leucyl-leucyl-phenylalanyl-nor-leucyl-tyrosyl-lysine, with high specificity and great avidity. Light microscopic autoradiography was used to visualize the binding and subsequent cellular processing of the formylhexapeptide N-formyl-nor-leucyl-leucyl-phenylalanyl-nor-leucyl-[125I]tyrosyl-lysine to polymorphonuclear leukocytes (PMN) and monocytes from patients with epidermoid tumors of the head and neck. Surface-adherent leukocytes were exposed to 5 nM 125I-labeled hexapeptide for 15 minutes at 4 degrees C and were either fixed immediately or rinsed and then further incubated for 20 minutes at 37 degrees C prior to fixation. Cells underwent autoradiography, and silver grains associated with 400 cells were counted. There were no significant differences between the numbers of formylpeptide receptors on control and cancer patient PMN. However, there were significantly larger numbers of formylpeptide receptors (P less than .02) on cancer patient monocytes than on control monocytes. Cells that were allowed to process bound hexapeptide at 37 degrees C prior to fixation showed large decreases in the number of cell-associated silver grains. However, the amount of hexapeptide associated with PMN and monocytes treated in this way was the same for both control and tumor patients. In addition, histograms were plotted showing the amount of hexapeptide bound versus the frequency of cells at each level of binding. Examination of these histograms revealed that two major peaks or subpopulations occurred in each for neutrophils and monocytes from control patients. Histograms of grain counts for neutrophils and monocytes from tumor patients did not display two separate peaks of formylhexapeptide binding; instead, only one broad peak was evident. These observations indicated that: Tumor patient PMN expressed as many formylpeptide receptors as did control PMN, and tumor patient monocytes possessed significantly more receptors than did control monocytes. The disposition of formylpeptide initially bound to control and tumor patient leukocytes appeared to be essentially the same. Subpopulations existed in each control neutrophil and monocyte sample, one exhibiting approximately 30% more formylpeptide binding than the other. However, in the leukocytes obtained from tumor patients, the distinction between these two subpopulations had become obscured such that only one cell population was evident.

Carcinoma, Squamous Cell↗