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PubMed1996

Monocyte chemotactic peptide-1 expression in acute and chronic human nephritides: a pathogenetic role in interstitial monocytes recruitment.

Tubulointerstitial damage is a common histopathological feature of acute and chronic renal diseases and a prognostic indicator of renal function outcome. Monocytes infiltrating the interstitium, through the release of cytokines and/or growth factors, may play a key role in the pathogenesis of tubulointerstitial damage. Monocyte chemotactic peptide-1 (MCP-1) is a specific and powerful chemoattractant and activating factor for monocytes. This study investigated MCP-1 expression and its correlation with monocyte infiltration and tubulointerstitial damage in biopsies of patients with acute interstitial nephritis (AIN) and a chronic glomerulonephritis, namely immunoglobulin. A nephropathy (IgAN), often characterized by tubulointerstitial involvement. Six patients with AIN and 20 patients with IgAN, nine with mild (G1 to 2) and 11 with moderate to severe histologic lesions (G3 to 5), were studied. MCP-1 gene and protein expression were evaluated by in situ hybridization and immunohistochemistry. Infiltrating CD68-positive cells were identified as monocytes. MCP-1, weakly expressed in normal kidneys, was clearly upregulated in AIN biopsies. The gene and the protein expression were primarily localized in tubular and glomerular parietal epithelial cells, as well as in infiltrating mononuclear cells. In IgAN, a striking increase in MCP-1 mRNA and protein expression was observed only in the biopsies with moderate to severe lesions, with a pattern of expression similar to AIN. The MCP-1 expression strictly correlated with monocyte infiltrates and tubulointerstitial damage. In addition, the urinary excretion of this chemokine was studied in 17 IgAN patients. MCP-1 protein concentration was higher, compared with healthy subjects, in IgAN patients, especially in the G3 to 5 group, and directly correlated with the renal MCP-1 gene expression. In conclusion, these data suggest that production of MCP-1 in the tubulointerstitial compartment may play a key role in modulating monocytes influx and, consequently, tubulointerstitial damage.

Acute Disease↗
PubMed2001

CD38 expression and functional activities are up-regulated by IFN-gamma on human monocytes and monocytic cell lines.

Human CD38, a surface molecule expressed by immature and activated T and B lymphocytes, has been characterized as a molecule transducing activation and proliferation signals, and intervening in adhesion to endothelium via its ligand CD31. CD38 is also a complex ectoenzyme featuring ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities, leading to the synthesis and degradation of cADPR, a Ca+-mobilizing agent. We investigated the effects of monocyte-activating stimuli (IFN-gamma, IL-2, LPS, TNF-alpha, and GM-CSF) on the expression and function of CD38, starting from the observation that human monocytes and the derived lines U937, THP-1, and Mono-Mac-6 bear the molecule on their surface. Our results indicate that IFN-gamma is a strong up-modulator of CD38, and IL-2 increases its expression only modestly. LPS, TNF-alpha, and GM-CSF had no detectable effects. Treatment with IFN-gamma produced a dose- and time-dependent up-regulation of CD38 in monocytes and monocytic lines, which was paralleled by increased ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities. Furthermore, CD38 ligation by specific MoAb reduced the IFN-gamma-dependent enhancement of monocyte-dynamic adhesion to endothelial monolayers. These findings identify IFN-gamma as a modulator of monocytic CD38 expression and indicate that CD38 plays a specific role in the activation and adhesion processes performed by monocytes.

ADP-ribosyl Cyclase↗
PubMed1992

Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes.

Monocytes play a critical role in defending the host against foreign organisms and in regulating the behavior of other cells. Monocytes circulate as nonadherent cells in the blood and migrate as adherent cells through tissues. Adhesion molecules mediate not only cell adhesion, but also migration, phagocytosis, and many other adhesion-dependent functions. Monocyte chemoattractant protein-1 (MCP-1) is thought to be responsible for monocyte recruitment in acute inflammatory conditions and may be an important mediator in chronic inflammation. In this study, immunofluorescence flow cytometry was used to determine whether MCP-1 can regulate the cell surface expression of adhesion molecules, particularly beta-2 and alpha-4 integrins and the leukocyte adhesion molecule-1. We found that MCP-1 induced expression of CD11c (p150,95 alpha-subunit) and CD11b (Mac-1 alpha-subunit), and caused little or no change of CD11a (lymphocyte function-associated Ag-1 alpha-subunit), very late activation Ag-4, or leukocyte adhesion molecule-1. We demonstrated that antibodies to beta-2 and alpha-4 integrins inhibited MCP-1-induced monocyte chemotaxis. We also showed that MCP-1 is capable of inducing IL-1 and IL-6, but not TNF production of monocytes. These results indicate that MCP-1 is not only a chemoattractant but also a novel cytokine with the capacity to regulate several parameters of monocyte function.

Antigens, CD↗
PubMed1992

Prolonged monocyte accumulation in the lung during bleomycin-induced pulmonary fibrosis. A noninvasive assessment of monocyte kinetics by scintigraphy.

It has become more evident that monocytes, macrophages, and their products interact in a complex manner with various cell types in the lung, and may under the proper set of conditions contribute to the pathogenesis of pulmonary fibrosis. Current methods used to assess the lung content of mononuclear cells, which include tissue immunohistochemistry and bronchoalveolar lavage fluid analysis, sample the lung at one point in time and therefore provide only a "snapshot" of dynamic process. We utilized external imaging (scintigraphy) to provide a dynamic assessment of the trafficking patterns of radiolabeled monocytes in the lungs of rabbits in conjunction with lung tissue morphometry and bronchoalveolar lavage fluid analysis to determine the kinetics of neutrophil and monocyte accumulation in the alveolar walls and alveolar spaces of the lung during bleomycin-induced pulmonary fibrosis. We found that scintigraphy accurately reflected the accumulation of monocyte-associated radioactivity in the alveolar walls over time as well as the subsequent migration of these cells into alveolar spaces during the acute phase of bleomycin-induced lung injury (days 0 to 14) when compared with lung tissue morphometry. The scintigraphy, lavage, and morphometry data together showed that neutrophil influx into both of these lung compartments preceded that of monocytes by days, and that the influx of monocytes accounted for a major proportion of mononuclear cells found in the alveolar walls and alveolar spaces of the lung during this acute phase of inflammation. The increased numbers of neutrophils and mononuclear cells in alveolar spaces normalized by days 14 and 28 respectively, but in contrast to the normalization of neutrophil content in alveolar walls by day 10, increased numbers of mononuclear cells persisted in alveolar walls for up to 56 days, a time when there was a significant increase in the hydroxyproline content of these lungs. These data also show that the increased number of mononuclear cells present in the alveolar walls on days 28 and 56 was not due to a persistent influx of blood monocytes. These data suggest: (a) that differential pathways of efflux existed for alveolar wall versus alveolar space mononuclear cells, (b) that a delay in efflux from the alveolar walls occurred and/or that an increase in the local proliferation of mononuclear cells in this compartment may have been occurring during the later phases of bleomycin-induced lung injury, and (c) that this prolonged residence of mononuclear cells in the alveolar walls occurred concurrently with the development of pulmonary fibrosis.

Animals↗
PubMed2003

[Study of monocyte intracellular cytokine and heterogeneity of monocytes in a gastric cancer patient].

It was previously reported that monocytes/macrophages play an important role in mediating T-cell dysfunction in tumor-bearing hosts, in which monocytes/macrophages were found to induce the loss of T-cell functions concomitantly with induction of defects in T-cell signaling molecules. These observations encouraged us to investigate monocyte status in cancer-bearing hosts. We characterized peripheral blood monocytes in gastric cancer patients with advanced disease (n = 14), in those with early disease (n = 17) and in healthy individuals (n = 14), based on surface marker, oxygen-burst capacity, and intracellular cytokine status (IL-10 and IL-12). To clarify which mediators induced the characteristic differences of monocytes in cancer-bearing hosts, healthy donor-derived monocytes were co-incubated with the patients' plasma. Intracellular IL-10 and IL-12 status on monocytes in advanced disease was significantly increased in comparison with early disease or healthy individuals, while there were no differences in the surface marker or oxygen-burst capacity of monocytes. The plasma from the patients with advanced disease could induce increased intracellular IL-10 and IL-12 status in healthy monocytes. The phenomenon was significantly inhibited with neutralizing mAbs specific for VEGF.

Aged↗
PubMed1992

Interleukin-1 from baboon peripheral blood monocytes: altered response to endotoxin (lipopolysaccharide) and Staphylococcus aureus stimulation compared with human monocytes.

The baboon Papio ursinus does not elicit a febrile response upon injection with endotoxin, but fever is produced when injected with Staphylococcus aureus particles (Zurowsky, Y., H. Laburn, D. Mitchell, Can. J. Physiol. Pharmacol. 65, 1402-1407 (1987)). We address the question whether baboon peripheral blood monocytes produce interleukin-1 (IL-1) when stimulated with endotoxin or S. aureus particles in culture. Results show that little IL-1 biological activity was produced from endotoxin-stimulated baboon peripheral blood monocytes, compared with S. aureus-stimulated cells. Measurements of IL-1 beta by radioimmunoassay supported these data. This is contrary to data from human monocytes, which show greater sensitivity to endotoxin. Examination of IL-1 beta mRNA from endotoxin-stimulated and S. aureus-stimulated baboon monocytes, however, showed that more mRNA for IL-1 beta was present in endotoxin-stimulated monocytes than in cells stimulated with S. aureus. This illustrates the possibility that the production and/or the secretion of IL-1 beta is not as efficient in baboon monocytes as it is in human monocytes.

Animals↗
PubMed1989

Activation of human monocytes occurs on cross-linking monocytic antigens to an Fc receptor.

Murine mAb to CD13, CD14, and class II MHC, are able to mobilize calcium in normal human monocytes and enhance superoxide production in primed cells. Antibodies to CD35 (CR1) also cause a minor calcium response in some individuals. Antibodies to CD11a, CD11b, CD11c, CD15, CD17, CD18, and CD45 do not activate monocytes. The ability of mAb to cause monocyte activation is not only dependent on the Ag with which they react but also on the isotype of the antibodies and the individual from whom the monocytes were obtained. It is shown that this is because the mAb that activate monocytes do so by formation of Ag-antibody-FcR complexes. F(ab')2 fragments of mAb to CD13 and CD14 do not therefore activate monocytes even when cross-linked with F(ab')2 anti-mouse Ig but do so when cross-linked with intact anti-mouse Ig. These data indicate that activation via the FcR requires perturbation of this receptor but does not necessarily require cross-linking of one FcR to another. Antibody-coated particles or cells able to bind to cell surface receptors on monocytes other than the FcR would thus augment FcR-mediated activation.

Antibodies, Monoclonal↗
PubMed1989

Enhancing effect of human monocytic colony-stimulating factor on monocyte tumoricidal activity.

Human monocytic colony-stimulating factor (hM-CSF) enhances several effector functions of human peripheral blood monocytes. In this study, we investigated the effect of the Mr 85,000 form of hM-CSF on the tumoricidal activity of human monocytes against several leukemic cell lines using a 12-h chromium release assay. Human peripheral blood monocytes preincubated with hM-CSF for 48 h showed more effective killing activity towards K562, U937, Daudi, and HL60 cells as compared with the cells preincubated with medium alone. Maximal enhancement of the tumoricidal activity was achieved by hM-CSF at concentrations of 50-100 ng/ml. A trace amount of lipopolysaccharide contained in the hM-CSF did not seem to contribute to the enhancing effect, as the addition of a lipopolysaccharide-neutralizing agent, polymyxin B, to the preincubation mixture did not reduce this effect. Anti-tumor necrosis factor antiserum partially blocked the tumoricidal activity mediated by hM-CSF, indicating that tumor necrosis factor may participate in the hM-CSF-mediated increase of monocyte tumor cell-killing activity. These results suggest that in addition to other monocyte-activating factors, hM-CSF augments monocyte tumoricidal activity against a wide spectrum of tumor targets.

Cell Line↗
PubMed1988

Stimulation of EBV-activated human B cells by monocytes and monocyte products. Role of IFN-beta 2/B cell stimulatory factor 2/IL-6.

EBV infects human B lymphocytes and induces them to proliferate, to produce Ig, and to give rise to immortal cell lines. Although the mechanisms of B cell activation by EBV are largely unknown, the continuous proliferation of EBV-immortalized B cells is dependent, at least in part, upon autocrine growth factors produced by the same EBV-infected B cells. In the present studies we have examined the influence of monocytes on B cell activation by EBV and found that unlike peripheral blood T cells and B cells, monocytes enhance by as much as 30- to 50-fold virus-induced B cell proliferation and Ig production. Upon activation with LPS, monocytes secrete a growth factor activity that promotes both proliferation and Ig secretion in EBV-infected B cells and thus reproduces the effects of monocytes in these cultures. Unlike a number of other factors, rIFN-beta 2/B cell stimulatory factor 2 (BSF-2)/IL-6 stimulates the growth of human B cells activated by EBV in a manner similar to that induced by activated monocyte supernatants. In addition, an antiserum to IFN-beta that recognizes both IFN-beta 1 and IFN-beta 2 completely neutralizes the B cell growth factor activity of activated monocyte supernatants. These findings demonstrate that IFN-beta 2/BSF-2/IL-6 is a growth factor for human B cells activated by EBV and suggest that this molecule is responsible for B cell growth stimulation induced by activated monocyte supernatants. We have examined the possibility that IFN-beta 2/BSF-2/IL-6 might also be responsible for B cell growth stimulation by supernatants of EBV-immortalized B cells and thus may function as an autocrine growth factor. However, IFN-beta 2/BSF-2/IL-6 is not detectable in supernatants of EBV-immortalized B cells by immunoprecipitation. Also, an antiserum to IFN-beta that neutralizes IFN-beta 2/BSF-2/IL-6 fails to neutralize autocrine growth factor activity. This suggests that autocrine growth factors produced by EBV-immortalized B cells are distinct from IFN-beta 2/BSF-2/IL-6. Thus, the continuous proliferation of EBV-immortalized B cells is enhanced by either autocrine or paracrine growth factors. One of the mediators with paracrine growth factor activity is IFN-beta 2/BSF-2/IL-6.

B-Lymphocytes↗
PubMed1989

Monocyte long-term cultivation on microvascular endothelial cell monolayers: morphologic and phenotypic characterization and comparison with monocytes cultured on tissue culture plastic.

Human monocytes were cultured on monolayers of a newly established microvascular endothelial cell strain. As compared to monocytes cultured on plastic, these endothelium-"derived" monocytes (EDM) showed distinct morphology, higher motility, and different antigen-expression pattern for several surface markers, as detected by cytofluorimetry. The MO-1- and the Leu-M1-marker were maintained on EDMs while they were lost on plastic-cultured cells. The MAX 1-26-termed markers failed to increase on EDMs, in contrast to plastic-cultured monocytes. For seven additional markers, expression after two weeks in vitro was higher on EDMs than on plastic-cultured monocytes. Functionally EDMs showed typical monocyte/macrophage behavior and were easily removable from the culture system for further experimentation. Our data suggest that monocytes cultured on microvascular endothelial cells are maintained for several weeks in a more physiologic state than monocytes cultured on plastic.

Animals↗
PubMed1988

Regulation of interleukin-6 expression in cultured human blood monocytes and monocyte-derived macrophages.

A culture system that allows human blood monocytes to differentiate into macrophages in vitro was used to study B-cell stimulatory factor-2/interleukin-6 (interferon-beta 2/26 kd protein) expression in mononuclear phagocytes. Using B-cell stimulatory factor-2 (BSF-2) cDNA and a polyclonal, monospecific antibody directed against human BSF-2, we find that strong interleukin-6 (IL-6) expression is initiated in cultured monocytes on stimulation with endotoxin. Maximally induced monocytic BSF-2/IL-6 synthesis (1% to 2% of total proteins secreted by monocytes) is more than ten times stronger than in terminally differentiated macrophages (approximately 0.1% of total secretory proteins). BSF-2/IL-6 mRNA was detectable as early as one hour after stimulation with endotoxin, reaching maximum levels three hours after stimulus. Interleukin-1 (IL-1) was able to stimulate IL-6 synthesis in monocytes, but not in macrophages. Tumor necrosis factor, interferon-gamma and interleukin-2 (IL-2) had no effect on IL-6 synthesis in monocytes or macrophages. We found five molecular weight forms of BSF-2/IL-6 to be secreted by monocytes of 21.5 kd, 23.5 kd, 24 kd, 26 kd, and 28 kd apparent molecular weight. The 26 kd and 28 kd forms were found to represent N-glycosylated molecules, which were not detectable on treatment of the cells with the N-glycosylation inhibitor tunicamycin. The 21.5 kd, 23.5 kd, and 24 kd BSF-2/IL-6 forms were unaffected by tunicamycin treatment. We conclude from our data that cells of the mononuclear phagocyte lineage are one of the main sites of BSF-2/IL-6 (interferon-beta 2/26 kd protein/HSF) synthesis.

Cell Differentiation↗
PubMed1986

A monoclonal antibody specific for a monocyte-macrophage membrane component blocks the human monocyte response to migration inhibitory factor.

In our study of the human monocyte response to migration inhibitory factor (MIF), we screened murine anti-monocyte monoclonal antibodies (MAb) for their ability to affect the MIF response. When blood monocytes were preincubated for 30 min at 37 degrees C with MAb of various cell specificities, it was found that Mo3e-MAb could inhibit the monocyte response to MIF. This effect was observed at an antibody concentration of 0.37 microgram/10(6) monocytes. This blocking activity appeared to be specific for Mo3e-MAb, since MAb specific for Mo1, Mo2, Mo4, alveolar macrophage (PAM-1), and platelet (Plt-1) antigens were unable to block the MIF response. Specificity was also shown by experiments performed with MAb similar to Mo3e-MAb in their immunofluorescence staining patterns. Two MAb of this type were not able to block the MIF response. All of these MAb are of the IgM isotype, and therefore it is unlikely that the blocking activity of Mo3e-MAb is mediated by the Fc receptor. These studies suggest that Mo3e-MAb may represent an anti-MIF receptor antibody. Mo3e-MAb recognizes a protease-sensitive antigen of 80 kD and 50 kD that is weakly expressed on fresh blood monocytes but is up-modulated by stimulation of monocytes with bacterial lipopolysaccharide, muramyl dipeptide, or phorbol compounds. Mo3e is also expressed by human myeloid cell lines, U-937 and HL-60, that have been stimulated in culture by biologically active phorbol diester compounds.

Antibodies, Monoclonal↗
PubMed1985

The kinetics of the production of granulocyte-monocyte colony stimulating activity (GM-CSA) by isolated human monocytes: response to bacterial endotoxin.

When mononuclear phagocytes are stimulated by bacterial endotoxins, they produce Granulocyte-Monocyte Colony-Stimulating Activity (GM-CSA). In order to study the kinetics of the production of GM-CSA by human monocytes, we prepared suspensions of these cells and studied their response to Salmonella typhi endotoxin. We found that when human monocytes were exposed to this preparation of endotoxin, they synthesized GM-CSA de novo and subsequently secreted it into the extracellular environment; however, within hours, the cells became highly refractory to further stimulation by endotoxin. The resistance to endotoxin which these cells rapidly acquired in vitro could not be accounted for by cell attrition, the accumulation of toxic metabolites in the cultures, negative feedback inhibition by newly synthesized GM-CSA, depolarization of the plasma membrane of the cells, or by degradation of endotoxin. When we studied the binding of tritium-labeled endotoxin to viable monocytes, we found that after monocytes were initially exposed to endotoxin, their subsequent ability to bind lipopolysaccharide molecules onto the surface of the plasma membrane was reduced. When we subjected concentrated supernates from endotoxin-stimulated monocyte cultures to gel filtration and isoelectric focusing, we noted that GM-CSA derived from human monocytes had an apparent molecular weight of approximately 42,000 daltons. Our results indicate that resistance to bacterial endotoxins acquired by mononuclear phagocytes may play a role in the immunologic phenomenon of immediate endotoxin tolerance observed in vivo and may in part be due to down-regulation of endotoxin binding to the outer surface of the cell.

Cells, Cultured↗
PubMed1983

Effect of human monocyte killing of tumour cells of antibody raised against an extracellular monocyte cytotoxin.

Human monocytes can kill or inhibit the growth of certain tumour cell lines. Amongst the possible mediators is a cytotoxin synthesized in readily detectable amounts by endotoxin-stimulated monocytes. A neutralizing antiserum to the cytotoxin has been used to assess the cytotoxin's contribution to monocyte killing of tumour cells. The antiserum was tested for possible inhibition of monocyte killing of three tumour cell lines--L929, K562 and A549. Inhibition was complete with L929, partial with K562 and insignificant with A549. Thus the contribution of the cytotoxin to monocyte killing of tumour cells depends upon the tumour line under test. Antibody against endotoxin-induced cytotoxin also neutralized cytotoxin induced in monocytes by other agents including BCG, Corynebacterium parvum, pokeweed mitogen and zymosan. Cytotoxin could be quantitatively removed from monocyte supernatants by Sepharose-bound, anticytotoxin antibody. Recovery of the cytotoxin from the immunoadsorbent was difficult because of its lability in the solutions commonly used for desorption. The best recovery has been achieved with 2 M urea, 2 M MgCl2 giving a 25% yield and a forty-fold increase in purity in a single step.

Adenocarcinoma↗
PubMed1983

Characterization of monocyte maturation in adherent and suspension cultures and its application to study monocyte differentiation in Hodgkin's disease.

Monocytes purified with cell scatter monitored counterflow centrifugation were cultured in plastic (adherent) and in teflon culture bags (suspension). Sequential changes were monitored during 15 days by measuring intracellular activity of three enzymes of intermediary metabolism: glucose-6-phosphate dehydrogenase (G-6-PDH), phosphohexose isomerase (PHI) and isocitrate dehydrogenase (ICDH), and the two acid hydrolases: acid phosphatase (ACP) and N-acetyl-beta-glucosaminidase (NAG). In teflon grown macrophages a significantly lower G-6-PDH activity was seen after 15 days in comparison to plastic adherent macrophages (P less than 0.0002). For the other enzymes similar values for both culture modalities were found. The significantly, cycloheximide insensitive, higher values for G-6-PDH, PHI and ICDH in 2 h plastic adherent monocytes in comparison with plastic non-adherent monocytes, suggest a relationship between adherent capacity and the level of intermediary metabolism. The overall yield of plastic adherent macrophages after 15 days was 35% in contrast with 89% for the in suspension cultured macrophages. This corroborates the existence of adherent and non-adherent monocytes, both capable of differentiation in vitro. In 14 patients with advanced Hodgkin's disease (HD) and 14 normal controls, monocyte differentiation was studied applying both culture modalities. The enzyme levels, reflecting growth and intermediary metabolism, were similar for both groups. The adherent capacity and yield, both in teflon and in plastic, after 15 days was comparable for both groups. It was concluded that in vitro monocyte differentiation in the presence of autologous serum was qualitatively and quantitatively normal in advanced HD; this is in favour of an intrinsically normal function of monocytes in HD.

Adolescent↗
PubMed1984

Cathepsin G in human mononuclear phagocytes: comparisons between monocytes and U937 monocyte-like cells.

Previous studies demonstrating that a continuous line of human monocyte-like cells (U937) and human monocytes contain elastase probably identical to human neutrophil elastase suggested the possibility that mononuclear phagocytes share other proteinases with neutrophils. The present work establishes that U937 cells contain cathepsin G, an enzyme heretofore found only in neutrophils. U937 cells contain approximately 10 micrograms of cathepsin G-like activity per 10(7) cells, about 25% of the cathepsin G activity in human neutrophils. Normal monocytes have minimal cathepsin G-like activity (approximately 0.1 microgram per 10(7) cells). The cathepsin G-like activity of U937 cells appears to be due to an enzyme that is the same as cathepsin G by several criteria: 1) it is a serine proteinase with activity like cathepsin G against a synthetic chymotrypsin substrate, succinyl-ala-ala-pro-phe-p-nitroanilide; 2) the proteolytic fragments it releases from fibronectin match those released by cathepsin G; 3) like cathepsin G, it can be purified by sequential Trasylol-Sepharose affinity chromatography and carboxymethyl-Sephadex ion exchange chromatography; 4) its amino acid composition and migration on SDS-polyacrylamide gel electrophoresis are indistinguishable from cathepsin G; and 5) it binds with antiserum raised to cathepsin G. The presence of cathepsin G in U937 cells, in much higher concentration than in normal monocytes, indicates either that the content of cathepsin G in monocytes decreases markedly during monocyte differentiation or that U937 cells differ from normal immature monocytes with respect to synthesis of this neutral proteinase.

Amino Acids↗
PubMed1981

Increased Fc receptor activity in monocytes from patients with rheumatoid arthritis: a study of monocyte binding and catabolism of soluble aggregates of IgG in vitro.

We studied the binding and catabolic function of adherent monocytes from patients with rheumatoid arthritis (RA) and normal subjects using stable, heat aggregates of IgG125I (A-IgG) as a model for soluble immune complexes. Scatchard plots of 4 degrees C binding data showed that RA monocytes had increased binding avidity and higher maximal binding capacity for A-IgG compared with monocytes from normal subjects. These data suggest that RA monocytes have increased numbers of Fc receptors for IgG, although a concomitant increase in the avidity of individual Fc receptors could not be excluded. At 37 degrees C, RA monocytes; kinetic analysis suggested that increases in catabolized A-IgG were due to increased binding of A-IgG with no change in the fractional rates of catabolism. Latex titers of RA patients correlated with the number of Fc receptors detected on RA monocytes. Mononuclear phagocytes from RA patients are often exposed to endogenous immune complexes that may be present in the blood of such patients; immune complexes may stimulate monocytes and possibly other mononuclear phagocytes to increase their capacity to bind and catabolize soluble immune complexes.

Adult↗
PubMed1995

Production of chemokines, interleukin-8 and monocyte chemoattractant protein-1, during monocyte: endothelial cell interactions.

The extravasation of leukocytes from the lumen of the vessel to a site of inflammation requires specific binding events. The interaction of leukocytes with endothelium, via specific receptors, may provide intracellular signals that activate extravasating cells. In the present study, we have investigated the production of chemokines, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) during monocyte: endothelial cell interactions. Both unstimulated and interferon-gamma (IFN-gamma)-prestimulated human umbilical vein endothelial cells (HUVEC) produced low constitutive levels of IL-8 and MCP-1. The addition of enriched monocytes with unstimulated HUVEC resulted in synergistic increases in production of both IL-8 and MCP-1. Monocytes cultured with IFN-gamma-preactivated HUVECs demonstrated little additional increase in IL-8 and MCP-1 production in coculture assays compared with unstimulated HUVEC. Northern blot analysis paralleled the protein data, demonstrating upregulated expression of IL-8 and MCP-1 mRNA in stimulated and unstimulated coculture assays. Culture of enriched monocytes and endothelial cells in transwells demonstrated no increases in IL-8 or MCP-1, indicating the necessity for cellular contact for chemokine production. In previous investigations, we have demonstrated that increased monocyte-derived MIP-1 alpha production was induced by intracellular adhesion molecule-1 (ICAM-1) interactions on activated HUVECs. In contrast, addition of anti-ICAM-1 monoclonal antibodies (MoAbs) did not diminish the production of IL-8 and MCP-1 in the present study. Furthermore, neither antibodies to IL-1 nor tumor necrosis factor (TNF) diminished the production of either IL-8 or MCP-1. However, when soluble matrix proteins were added to the coculture to block cellular interactions, the chemokine protein and mRNA levels were significantly decreased. IL-8 production was decreased by both soluble collagen and fibronectin, whereas MCP-1 was decreased by only soluble collagen, suggesting differential activation pathways. These results indicate that IL-8 and MCP-1 production are increased during monocyte and endothelial cell interactions in part due to matrix protein binding mechanisms. This mechanism may serve a role in cell activation, production of chemokines, as well as extravasation and recruitment of additional leukocytes during inflammatory responses.

Antibodies, Monoclonal↗