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PubMed1992

Monocyte adherence to fibronectin: role of CD11/CD18 integrins and relationship to other monocyte functions.

Adherence of monocytes to extracellular matrix components is critical for their accumulation at sites of infection. To gain insight into the factors that regulate monocyte recruitment, we have studied monocyte adherence with regard to the regulatory effects of bacterial lipopolysaccharide (LPS) and the mechanisms involved; moreover, we have contrasted the phenotypes of adherent and nonadherent cells. Our results show that only a minor subpopulation of monocytes (20-25%) adhere spontaneously to fibronectin and that LPS stimulated a threefold increase in the proportion of adherent cells. Basal adherence and LPS-stimulated adherence of monocytes to fibronectin were substantially mediated by CD11/CD18 integrins. Further studies revealed that spontaneously adherent monocytes were 14-fold more actively phagocytic, released 1.6-fold more superoxide anion, and contained 20-fold more peroxidase activity than nonadherent cells, whereas LPS-adherent cells had an intermediate phenotype. These results indicate that LPS may enhance the accumulation of monocytes with an antimicrobial phenotype and thereby promote resolution of tissue infection.

Antigens, CD↗
PubMed1995

Monocytes cultured in cytokine-defined environments differ from freshly isolated monocytes in their responses to IL-4 and IL-10.

To investigate the regulatory effects of the prototypic Th2 lymphocyte products and potential immunotherapeutic agents interleukin-4 (IL-4) and IL-10 on macrophages differentiated in vitro under different cytokine-defined environments, blood monocytes were incubated for 7 days in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor or IL-4. The effect of monocyte culture in the presence or absence of serum was also investigated. Functional responses by 7-day-cultured cells to IL-4, quantified as decreased CD14 expression and suppression of lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) and IL-1 beta production, and as a positive response, increased CD23 expression, were compared directly with the responses by monocytes from which they were derived. In response to IL-10, decreases in LPS-induced TNF-alpha and IL-1 beta production and reduction in the expression of major histocompatibility complex (MHC) class II antigens were examined. Seven-day cultured monocytes/macrophages showed (1) diminished TNF-alpha production in response to IL-10 but not IL-4 (2), diminished IL-1 beta production in response to both IL-4 and IL-10, and compared with fresh monocytes (3), diminished CD14 expression in response to IL-4, and (4) a lesser increase in CD23 expression in response to IL-4. This was the case regardless of the cytokine in the presence of which the cells had been cultured for 7 days. Monocytes cultured for 7 days in GM-CSF expressed increased levels of MHC class II and LPS-induced TNF-alpha and responded inefficiently to IL-10 for decreased MHC class II. The responses by monocytes cultured for 7 days with GM-CSF resemble the published properties of synovial fluid macrophages from patients with chronic inflammatory arthritis. The study highlights the complexity of monocyte/macrophage responses to the immunoregulatory cytokines IL-4 and IL-10 and concludes that responses to IL-4 and IL-10 by blood monocytes may not be representative of responses by their differentiated or activated counterparts.

Antigens, CD↗
PubMed1991

Monocyte zinc and in vitro prostaglandin E2 and interleukin-1 beta production by cultured peripheral blood monocytes in patients with Crohn's disease.

This study investigated the relationship between zinc status and prostaglandin E2 and interleukin-1 beta production by cultured monocytes in patients with Crohn's disease. Monocyte zinc was significantly decreased in both 12 inpatients and 22 outpatients compared with controls (P less than 0.001) but lymphocyte and polymorphonuclear cell zinc were normal. When cultured monocytes from 10 outpatients with Crohn's disease were stimulated with lipopolysaccharide, prostaglandin E2 production increased markedly, coupled with a fall in monocyte zinc. In matched controls, prostaglandin E2 production was significantly less and monocyte zinc remained stable. No difference in interleukin-1 release was noted between patients and controls. The addition of prednisolone to cell cultures suppressed prostaglandin E2, interleukin-1 synthesis, and monocyte zinc did not change. Zinc chloride augmented prostaglandin E2 production in patients, but not controls, and interleukin-1 remained stable. These results demonstrate a link between low monocyte zinc concentration and excessive prostaglandin production in patients with Crohn's disease.

Cells, Cultured↗
PubMed2001

Monocyte-chemoattractant-protein-1-mediated migration of human monocytes towards blasts from patients with acute myeloid leukemia.

PURPOSE: In the present study the possible clinical relevance of monocyte chemoattractant protein (MCP)-1 in patients with acute myeloid leukemia (AML) was established. METHODS: The pattern of migration of human monocytes towards the supernatants of blasts from 15 patients with AML was studied and the role of MCP-1, produced by these blasts, was assessed. RESULTS: In 4 patients (group 1) the amount of monocyte migration was low and not inhibited by the addition of anti-hMCP-1. In 11 patients, the amount of monocyte migration was high; after addition of anti-hMCP-1, monocyte migration was either completely (8 patients, group 2), or partly or not (3 patients, group 3) inhibited to the level of chemokinesis. In groups 1 and 2, there was a good correlation (r = 0.67) between the concentration of MCP-1 in the supernatants and the amount of monocyte migration. In group 3, such a correlation was not evident, suggesting that another chemokine might be involved or MCP-1 function was impaired by an unknown substance. Finally, measurements of MCP-1 during culture of AML blasts showed that the time at which maximal amounts of MCP-1 are produced differs between the AML samples. CONCLUSIONS: AML blasts produce different amounts of MCP-1, which plays an important role in monocyte migration towards most AML blasts. Therefore, in the context of adoptive immunotherapy, MCP-1 might be involved in future tumor vaccination programmes using autologous MCP-1-transfected irradiated AML blasts.

Cancer Vaccines↗
PubMed1980

Purification of human monocytes: isolation and collection of large numbers of peripheral blood monocytes.

Monocytes from human peripheral blood were purified by elutriation centrifugation. Up to 1.5 x 10(9) peripheral blood mononuclear cells could be separated in isotonic media to yield 6--8 x 10(8) lymphocytes with 95% purity and 1.5--2.5 x 10(8) monocytes with greater than 90% purity. The temperature at which elutriation was performed determined the purity of the monocyte fraction. Both the lymphocyte and monocyte fractions were characterized by cell sizing and histochemical staining. Most of the myeloperoxidase positive mononuclear cells (monocytes) had a modal volume of 378 micrometer 3 while 10% were within the modal volume of the lymphocytes, 131 micrometer 3. Thus, there are two populations of cells with histochemical properties of monocytes which are separable by size. The collection and isolation of human peripheral blood monocyte populations in large numbers will facilitate studies of their functional characteristics.

Cell Separation↗
PubMed1986

Monocyte activating factor in sarcoidosis. II. Secretion of the factor from monocytes.

The normal human monocytes pretreated with the monocyte activating factor found in sarcoidosis sera were shown to secrete a factor which induced normal human monocytes to spread as well as to increase their cell size. Phagocytosis and glucose consumption of normal human monocytes were also increased by this secondarily obtained factor. Its molecular weight was about 70,000. These results indicate that this secondary factor may be the same substance as the monocyte activating factor found in sarcoidosis sera. The normal human monocytes pretreated with the monocyte activating factor were also shown to liberate a factor which generated macrophage migration inhibitory factor in cooperation with normal human sera.

Animals↗
PubMed2006

Increased expression levels of monocyte CCR2 and monocyte chemoattractant protein-1 in patients with diabetes mellitus.

Increased monocyte recruitment into subendothelial space in atherosclerotic lesions is one of the hallmarks of diabetic angiopathy. The aim of this study was to determine the state of peripheral blood monocytes in diabetes associated with atherosclerosis. Diabetic patients treated with/without an oral hypoglycemic agent and/or insulin for at least 1 year were recruited (n=106). We also included 24 non-diabetic control subjects. We measured serum levels of monocyte chemoattractant protein (MCP)-1, fasting plasma glucose (FPG), HbA1c, total cholesterol, triglyceride, body mass index (BMI), high sensitivity CRP (hs-CRP) and evaluated CCR2, CD36, CD68 expression on the surface of monocytes. Serum MCP-1 levels were significantly (p<0.05) higher in diabetic patients than in normal subjects. In diabetic patients, serum MCP-1 levels correlated significantly with FPG, HbA1c, triglyceride, BMI, and hs-CRP. The expression levels of CCR2, CD36, and CD68 on monocytes were significantly increased in diabetic patients and were more upregulated by MCP-1 stimulation. Our data suggest that elevated serum MCP-1 levels and increased monocyte CCR2, CD36, CD68 expression correlate with poor blood glucose control and potentially contribute to increased recruitment of monocytes to the vessel wall in diabetes mellitus.

Cells, Cultured↗
PubMed2000

Peroxisome proliferator-activated receptor and retinoid X receptor ligands inhibit monocyte chemotactic protein-1-directed migration of monocytes.

Monocyte chemotactic protein-1 (MCP-1)-directed transendothelial migration of monocytes plays a key role in the development of inflammatory diseases. Infiltration of tissues by monocytes requires degradation of extracellular matrices, a process that involves matrix metalloproteinases. We studied the effects of peroxisome proliferator-activated receptor (PPAR) gamma, alpha, and retinoid X receptor alpha (RXRalpha) ligands on MCP-1-directed migration and matrix metalloproteinase expression of a human acute monocytic leukemia cell line (THP-1). PPARgamma ligands attenuated MCP-1-induced migration, with 50% inhibition (IC(50)) at 2.8 microM for troglitazone and 4.8 microM for rosiglitazone. PPARalpha ligands WY-14643 (IC(50): 0.9 microM) and 5,8,11,14-eicosatetranoic acid (IC(50): 9.9 microM), and the potent RXRalpha ligand AGN 4204 (IC(50): 3.6 nM) also blocked monocyte migration. Troglitazone, rosiglitazone, or AGN 4204 inhibited phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 expression. PPARalpha activators WY-14643 and 5,8,11,14-eicosatetraynoic acid, however, had no inhibitory effect. AGN 4204 increased PMA-induced tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) expression, whereas all PPAR ligands showed no effect. All PPAR and RXRalpha ligands blocked chemotaxis of THP-1 monocytes in the absence of a matrix barrier. This study demonstrates that activated PPARs and RXRalpha, block MCP-1-directed monocyte migration, mediated, at least in part, through their effects on matrix metalloproteinase-9 or TIMP-1 production, or chemotaxis.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1998

Establishment of a stable HL60 subline having the potential for monocytic differentiation using granulocyte-macrophage colony-stimulating factor: possible use for the study of monocytic differentiation and oxidative stress.

A stable HL60 subline having the potential for monocytic differentiation was established by use of GM-CSF. HL60, a human promyelocytic cell line, has frequently been employed for research in the fields of monocytic differentiation and atherosclerosis because of its potential to differentiate into either granulocytes or monocytes. However, HL60 are frequently seen to change their phenotype during long-term culture. To date, many sublines or variants of HL60 cells have been established. However, most of them display diminished or complete loss of activities that characterize parental cells. The present study was conducted to establish a stable HL60 subline with the potential for monocytic differentiation. Firstly, a single HL60 cell was isolated by limiting dilution, and was successfully proliferated by incubation with GM-CSF. Secondly, from this population, cells were selected that had the ability to generate superoxide after VD-induced monocytic differentiation. Cells obtained in this manner (designated HL60/DU-1) exhibited expression of CD14 and CD11b and suppression of CD3 expression after monocytic differentiation. NBT positivity showed a consistent level of over 971% after a 6-day challenge with VD throughout the experimental period of 12 months. HL60/DU-1 cells, which were cryopreserved in liquid nitrogen for 6 months, thawed and re-cultured, exhibited over 97% NBT positivity. Carvedilol and probucol, which exhibit antioxidative activity, inhibited superoxide release from the differentiated HL60/DU-1 cells. HL60/DU-1 cell line is a promising model for the study of monocytic differentiation and the effects of oxygen radicals.

Calcitriol↗
PubMed1998

The effects of bovine respiratory syncytial virus on the phagocytic and antigen-presenting capacity of peripheral blood monocytes and monocytic cell lines derived from lambs and calves.

Human respiratory syncytial virus and bovine respiratory syncytial virus (BRSV) suppress lymphocyte responses to mitogens. In the present study, the possible effects of BRSV on some functions of antigen-presenting cells (APC) were investigated by exposing ovine monocytic cells to the virus before their use as APC. The depletion of monocytes from peripheral blood mononuclear cells resulted in the near total abrogation of proliferative responses to phytohaemagglutinin (PHA). Reactivity was restored by the addition of homologous monocytic cells derived from ovine peripheral blood monocytes as APC. The exposure of these monocytic cells to BRSV for 48 h before their use as APC significantly reduced the proliferative responses of uninfected ovine lymphocytes to PHA. Furthermore, the exposure of bovine peripheral blood monocytes and bovine and ovine monocytic cell lines to BRSV for 48 h reduced their capacity to phagocytize latex beads.

Animals↗
PubMed1999

T lymphocytes downregulate granulocyte-macrophage colony-stimulating factor secretion from stimulated monocytes by increasing the secretion of monocyte-derived interleukin-10.

In previous studies we characterized the cytokine regulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) secretion by endothelial cells and monocytes and found differences in secretion pattern within and between these cell systems. In this study, the regulatory effect of T lymphocytes on CSF secretion was examined. T lymphocytes had no effect on CSF secretion by endothelial cells. In contrast, the addition of T lymphocytes significantly and dose dependently downregulated GM-CSF, but not G-CSF, secretion by monocytes. In one of our previous studies it was shown that interleukin-4 (IL-4) and interleukin-10 (IL-10) were the most potent inhibitory cytokines of CSF secretion by monocytes. Both these cytokines are produced by T lymphocytes. However, the downregulating effect on monocyte GM-CSF secretion was not due to increased secretion of T-lymphocyte-derived IL-4 or IL-10. Instead, the presence of T lymphocytes increased the secretion of monocyte-derived IL-10. It was shown earlier than IL-10 regulates CSF secretion by monocytes in an autocrine manner. Our data indicate that T lymphocytes might interfere with this autocrine regulation and thereby influence monocyte function in immune response and cell proliferation.

Cells, Cultured↗
PubMed2001

Homocysteine stimulates the expression of monocyte chemoattractant protein-1 in endothelial cells leading to enhanced monocyte chemotaxis.

Hyperhomocysteinemia has been identified as an independent risk factor for atherosclerosis. The infiltration of monocytes into the arterial wall is one of the key events during atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates the migration of monocytes into the intima of the arterial wall. The mechanism by which increased monocyte infiltration occurs in atherosclerotic lesions in patients with hyperhomocysteinemia has not been delineated. The objective of the present study was to investigate the effect of homocysteine on MCP-1 production in endothelial cells. Cells were incubated with homocysteine. The secretion of MCP-1 protein was significantly increased (195% as compared to the control) in cells treated with pathological concentrations of homocysteine. Such effect was accompanied by an increased expression of MCP-1 mRNA (176% as compared to the control) in endothelial cells which resulted in enhanced monocyte chemotaxis. The p38 MAP kinase as well as other members of the p38 MAP kinase pathway, including MKK3, MKK6, ATF-2 and Elk-1, were activated in homocysteine-treated cells. Homocysteine-induced MCP-1 expression and subsequent monocyte chemotaxis were blocked by a p38 MAP kinase inhibitor (SB203580) suggesting that the p38 MAP kinase pathway might be involved in homocysteine-induced MCP-1 expression in endothelial cells. In contrast, staurosporine, a protein kinase C inhibitor, had no effect on homocysteine-induced MCP-1 expression. In conclusion, our results indicate that homocysteine stimulates MCP-1 expression in endothelial cells leading to enhanced monocyte chemotaxis.

Activating Transcription Factor 2↗
PubMed1998

Difference in the blood monocyte phenotype between uremic patients and healthy controls: its relation to monocyte differentiation into macrophages in the peritoneal cavity.

The phenotypic alterations between blood monocytes from 11 patients with end-stage renal disease, who had been on peritoneal dialysis for less than one week, and blood monocytes from 10 healthy controls, were analyzed. In addition, peritoneal macrophages in the dialysate effluent were enclosed. Analysis of functional receptor density was performed using immunostaining and flow cytometry. The phenotypic characterization was selected to represent various biological functions such as adhesion, phagocytosis (CD11b/CD18, CD11c/CD18, CD16), antigen-presentation (HLA-DR, ICAM-1), differentiation (transferrin receptor, CD71), receptor for LPS (CD14) and initiation of the coagulation cascade (Tissue factor, CD142). The proportion of CD16-positive blood monocytes and the quantitative level of ICAM-1 were higher in the patient group, compared to healthy controls. A significant increase in the quantitative level of CD11b/CD18, CD11c/CD18, HLA-DR and ICAM-1, transferrin receptor, CD14 and CD16, was found on peritoneal macrophages, compared to monocytes, harvested both from the corresponding patients, as well as from healthy donors. In contrast, we did not find any significant differences in the expression of tissue factor between monocytes and peritoneal macrophages. In conclusion, phenotypic differences exist between monocyte populations in the blood circulation of CAPD patients, and healthy individuals. We also show that transmigration of monocytes into the peritoneal cavity implies a selective up-regulation of functional receptors, preferentially related to adhesion, and antigen-presentation in a steady-state situation in non-infected CAPD patients.

Adult↗
PubMed1978

Monocytes and macrophages in malignant melanoma. II. Lysis of antibody-coated human erythrocytes as an assay of monocyte function.

Peripheral blood mononuclear cells will lyse antibody-treated human erythrocytes. Using Group A red cells and a hyperimmune anti-A1 serum, we have devised a microassay for the cytolytic capacity of mononuclear cell suspensions. The effector cells responsible for red-cell lysis are mononuclear, adherent and phagocytic, and their activity is blocked by aggregated IgG. Their presence correlates well with non-specific esterase-containing cells and we conclude that they are monocytes. Dose-response curves of red-cell lysis plotted against numbers of monocytes were used to derive a simple parameter expressing the number of monocytes needed to lyse 15% of the 51Cr-labelled red cells. The assay was applied to a group of 27 normal controls and 36 patients with a histologically proven diagnosis of malignant melanoma. The results indicate that monocytes from patients show significantly greater lytic activity than those from the controls. These data suggest that monocytes from cancer patients are in some way activated, and that other defects in monocyte function which have been detected in cancer patients (defective chemotaxis and maturation) may be associated with monocyte "activation".

Antibody-Dependent Cell Cytotoxicity↗
PubMed2000

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has opposing effects on the capacity of monocytes versus monocyte-derived dendritic cells to stimulate the antigen-specific proliferation of a human T cell clone.

GM-CSF is widely used in combination with IL-4 to differentiate monocytes into potent T cell stimulatory cells, referred to as monocyte-derived dendritic cells (MoDC). These cytokines further increased the stimulatory function of MoDC when present during their incubation with antigen, as determined by the proliferative response of an allergen-specific T cell clone. Conversely, the incubation of freshly isolated monocytes with antigen in the presence of GM-CSF or GM-CSF and IL-4 strongly inhibited the specific stimulation of the T cells, compared with monocytes pulsed in the absence of cytokines. This suppression was partly due to the secretion of prostaglandin E2 (PGE2) and IL-10 by GM-CSF-treated monocytes, since the combined use of indomethacin and anti-IL-10 antibodies during GM-CSF incubation and antigen pulsing restored T cell growth to about 65% of control levels. As confirmed by culture supernatant transfer experiments, maximal inhibition of T cell stimulation was also dependent on the direct contact between the T cells and GM-CSF-treated monocytes during antigen presentation. Collectively, these results imply that GM-CSF can either inhibit or enhance the re-stimulation of primed T cells by antigen-presenting monocytes or MoDC, respectively.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Human autologous monocytes and monocyte-derived macrophages in co-culture with carcinoma F-spheroids secrete IL-6 by a non-CD14-dependent pathway.

The secretion of interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)-alpha were compared when freshly isolated autologous monocytes or monocytederived macrophages (MDMs) were co-cultured in vitro with autologous fragment (F)-spheroids established from a series of head and neck squamous cell carcinoma (HNSCC) patients. F-spheroids were generated from the malignant tumour (M-spheroids) or from benign mucosa (B-spheroids) from which the tumour originated control. If monocytes maturated towards MDMs before co-culture, the IL-6 secretion declined dependent on the extent of the MDM maturation by both M- and B-spheroid stimulation. When MDMs maturated in continuous co-culture, a steady-state secretion of IL-6 continued for several days but diminished when the culture medium was changed every 24 h. No co-culture-induced IL-1 beta or TNF-alpha was determined. Both the cytokine secretion and the mRNA gene expression revealed a different monocyte/MDM activation when co-culture and lipopolysaccharide (LPS)-stimulation were compared. Addition of anti-CD14 (10 microg/ml) decreased monocyte LPS-stimulated, but increased monocyte co-culture stimulated IL-6 secretion. In conclusion, M- and B-spheroids similarly stimulated monocytes and to a lesser extent MDMs. MDMs that maturated with F-spheroids present, retained responsiveness at the monocyte level. Co-culture-induced monocyte stimulation, as measured by IL-6 secretion, was not dependent on activation via the CD14 molecule.

Carcinoma, Squamous Cell↗
PubMed2001

Monocyte integrin expression and monocyte-platelet complex formation in humans with coronary restenosis.

1. In the present study, we sought to determine whether patients with restenosis after coronary stenting possess increased monocyte reactivity, as manifested by a higher level of adhesion molecule expression and an enhanced propensity to form monocyte-platelet aggregates after activation in vitro. 2. Anti-coagulated peripheral venous blood from 24 patients, 10 with and 14 without angiographically verified restenosis, was obtained. Leucocyte antigen expression and the number of leucocyte-platelet complexes were measured by flow cytometry after activation in whole blood. 3. Surface integrin Mac-1 (CD11b/CD18) and VLA-4 (CD49d/ CD29) expression on monocytes and the relative number of monocyte-platelet complexes after in vitro activation were significantly elevated in patients with restenosis compared with patients without restenosis (fluorescence intensities of 1425 +/- 76 vs 1195 +/- 71, 87 +/- 7 vs 65 +/- 6 and 47 +/- 4 vs 29 +/- 3% for for Mac-1, VLA-4 and monocyte-platelet complexes, respectively; P < 0.05 for each parameter). 4. The results suggest that restenosis is associated with increased monocyte VLA-4 and Mac-1 integrin expression and monocyte-platelet complex formation, which can be revealed after activation in vitro.

Blood Platelets↗
PubMed2003

Coupling of contact sensitizers to thiol groups is a key event for the activation of monocytes and monocyte-derived dendritic cells.

Strong contact sensitizers are able to induce distinct signal transduction mechanisms in antigen-presenting cells by coupling to cell proteins. The predominant target structures of haptens are thought to be thiol and amino groups in cysteine and lysine residues. We studied whether coupling of small reactive chemicals to thiol or amino groups might be responsible for the activation of monocytes and mature monocyte-derived dendritic cells. Human peripheral blood mononuclear cells were stimulated in vitro with subtoxic concentrations of the strong haptens 5-chloro-2-methylisothiazolinone plus 2-methylisothiazolinone and 2, 4, 6-trinitrochlorobenzene, the thiol-reactive reagents N-hydroxymaleimide and N-ethylmaleimide, as well as the amino-reactive compounds sulfosuccinimidyl acetate and 2-iminothiolane. Flow cytometric quantification of tyrosine phosphorylation in CD14+ monocytes showed that 5-chloro-2-methylisothiazolinone plus 2-methylisothiazolinone, 2, 4, 6-trinitrochlorobenzene, N-hydroxymaleimide, and N-ethylmaleimide but not sulfosuccinimidyl acetate and 2-iminothiolane strongly induced this process. Tyrosine phosphorylation induced by 5-chloro-2-methylisothiazolinone plus 2-methylisothiazolinone and 2, 4, 6-trinitrochlorobenzene was completely prevented in the presence of cysteine but not lysine, suggesting a competitive mechanism between cysteine and sulfhydryl groups of cell proteins. Using the mouse ear swelling test N-hydroxymaleimide could be classified as a significant contact allergen in comparison to 2, 4, 6-trinitrochlorobenzene, whereas no sensitizing potential became apparent for sulfosuccinimidyl acetate and 2-iminothiolane. Western blot analysis on monocytes and mature monocyte-derived dendritic cells confirmed the flow cytometric data for tyrosine phosphorylation and demonstrated a selective capacity of haptens and thiol-reactive compounds to activate ERK1/2 mitogen-activated protein kinase. Our data show that strong affinity of a small reactive chemical toward thiol groups is important for the activation of monocytes and monocyte-derived dendritic cells and can support the process of sensitization.

Acetates↗