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PubMed1982

Numerical changes in blood monocytes in bronchial asthma.

Numerical changes in peripheral blood monocytes were examined in 125 patients with bronchial asthma using a new direct method of counting blood monocytes. The number of monocytes in non-attack stages of bronchial asthma was similar to that of healthy controls. The monocyte count observed in overall cases showed a significantly higher value both in pre-attack and attack stages than in non-attack stages. Changes in the number of monocytes in an individual spontaneous asthmatic cycle tended to increase in pre-attack stages, increase more markedly during asthma attacks, then to decrease after the attack was alleviated. Monocytes in cases with a positive test for bronchial challenge to house dust extract changed in almost the same manner as for spontaneous asthma attacks. The number of monocytes did not change during bronchospasm provoked by inhalation of acetylcholine. Exercise-induced asthma patients exhibited indefinite changes of monocytes; that is, some cases showed a significant increase in the number of monocytes related to the asthma cycle, but other cases did not show any appreciable change. These findings suggest that the number of monocytes in the peripheral blood may change in close relation to asthma attacks elicited by allergic reactions.

Adolescent↗
PubMed2005

Effect of neutrophil apoptosis on monocytic cytokine response to Porphyromonas gingivalis lipopolysaccharide.

BACKGROUND: Neutrophil apoptosis may play a critical role in the resolution of inflammation by stimulating anti-inflammatory cytokine generation from monocytes. In this study, we investigated the effect of apoptotic neutrophils on interleukin (IL)-10 and IL-1beta production from monocytes in response to Porphyromonas gingivalis lipopolysaccharide. METHODS: Peripheral blood neutrophils from healthy individuals were isolated by sodium diatrizoate density gradient centrifugation. In order to induce apoptosis, neutrophils were cultured for 24 hours in modified Dulbecco's medium supplemented with 10% autologous serum. Cell apoptosis was quantified by Annexin V positivity and loss of CD16 expression on the cell surface. Peripheral blood mononuclear cells were isolated from the same subjects; monocytes were purified by magnetic cell sorting and cultured with or without apoptotic or fresh neutrophils. Lipopolysaccharide from Porphyromonas gingivalis was used for cell stimulation. IL-1beta and IL-10 levels in supernatants were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-10 generation was significantly increased in monocytes cultured with apoptotic neutrophils compared to monocytes alone or cocultured with fresh neutrophils (P <0.05). IL-1beta was suppressed both in resting and lipopolysaccharide-stimulated monocytes in the presence of apoptotic neutrophils compared to monocytes alone or monocytes cultured with fresh neutrophils at all time points (P <0.05). CONCLUSION: Neutrophil apoptosis provides a signal to monocytes, changing the phenotype of the monocyte resulting in the production of anti-inflammatory cytokines and suppression of proinflammatory cytokines in response to lipopolysaccharide.

Adult↗
PubMed1999

The potential for monocyte-mediated immunotherapy during infection and malignancy--Part II: in vivo activation by exogenous cytokines and clinical applications.

The monocyte system exhibits a range of immunological mechanisms that may be harnessed for therapeutic effect against infection and malignancy. The advent of novel therapies aimed at treating infection and malignancy is complemented by a resurgence of clinical interest in immunotherapeutic programmes to treat diseases by modification or direct augmentation of host immunity. Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-gamma modulate the function of monocytes and have been used to experimentally probe the immunotherapeutic potential of monocytes against micro-organisms and malignancy. However, monocytes rarely act alone but communicate with other leukocytes involved in cell-mediated immunity. In particular monocytes cooperate with the T-helper (Th1 and Th2) sub-populations of peripheral lymphocytes. Moreover, sub-populations of monocytes, as identified by the co-expression of membrane-associated CD14 and CD16, have been shown to exist. At the preclinical level, this provides a unique opportunity to explore the effect of immunotherapeutic strategies on the function of monocyte sub-populations against infectious or malignant challenge and may allow immunotherapeutic strategies to be targeted towards specific monocyte sub-populations. Preclinical and clinical studies in human subjects suggest that GM-CSF and other cytokines such as IFN-gamma are the most promising biological response modifiers for augmenting monocyte-mediated immunity. In this review, the immunotherapeutic potential of the monocyte system will be discussed in the context of combating microbial and malignant disease.

Animals↗
PubMed2000

Human blood monocytes interact with type I collagen through alpha x beta 2 integrin (CD11c-CD18, gp150-95).

Human blood monocytes are attracted into connective tissues during early steps of inflammation and wound healing, and locally interact with resident cells and extracellular matrix proteins. We studied the effects of type I collagen on monocyte adhesion and superoxide anion production, using human monocytes elutriated from peripheral blood and type I collagen obtained from rat tail tendon. Both acid-soluble and pepsin-digested type I collagens promoted the adhesion of monocytes, whereas only acid-soluble collagen with intact telopeptides induced the production of superoxide. Adhesion and activation of monocytes on acid-soluble type I collagen depended on the presence of divalent cations. mAbs directed against integrin subunits CD11c and CD18 specifically inhibited adhesion and activation of monocytes on type I collagen. Protein membrane extracts obtained from monocytes were submitted to affinity chromatography on collagen I-Sepharose 4B, and analyzed by Western blotting using specific anti-integrin subunit Abs. In the case of both acid-soluble and pepsin-digested collagens, two bands were revealed with mAbs against CD11c and CD18 integrin subunits. Our results demonstrate that monocytes interact with type I collagen through CD11c-CD18 (alpha x beta 2) integrins, which promote their adhesion and activation. For monocyte activation, specific domains of the type I collagen telopeptides are necessary. Interactions between monocytes and collagen are most likely involved in the cascade of events that characterize the initial phases of inflammation.

Acids↗
PubMed2001

IL-10 inhibits granulocyte-macrophage colony-stimulating factor-dependent human monocyte survival at the early stage of the culture and inhibits the generation of macrophages.

We previously demonstrated that IL-10 alone does not stimulate growth and differentiation of human monocytes, but enhances those of monocytes stimulated with M-CSF. We studied here the effect of IL-10 on human monocytes stimulated with GM-CSF. Monocytes stimulated with GM-CSF alone survived and developed into macrophages. Monocytes cultured with GM-CSF plus IL-10, however, died through apoptosis. IL-10 decreased expression of bcl-2, bcl-x(L), and mcl-1- but not bax mRNA in monocytes stimulated with GM-CSF. IL-10 did not change the expression of mRNA of both GM-CSFR alpha-chain and beta-chain, but inhibited tyrosine phosphorylation of STAT5 and extracellular signal-regulated kinases 1 and 2 in the monocytes. The inhibitory effect of IL-10 was restricted to treatment 48 h after stimulation with GM-CSF. Addition of IL-10 after that time induced neither apoptosis nor a decrease in expression of bcl-2, bcl-x(L), and mcl-1 mRNA. IL-10, however, inhibited LPS-induced TNF-alpha production even in these cells, indicating that the cells still possessed responsiveness to IL-10. Monocytes pretreated for >48 h with GM-CSF became resistant to GM-CSF withdrawal, and the cells could survive without GM-CSF. These results indicate that IL-10 selectively inhibits GM-CSF-dependent monocyte survival by inhibiting the signaling events induced by GM-CSF, but the timing of addition of IL-10 is critical, and IL-10 had to be added within 48 h after stimulation with GM-CSF to achieve the inhibitory effect. These results taken together with our previous results indicate that IL-10 plays a pivotal role in monocyte survival and development into macrophages in concert with M-CSF and GM-CSF.

Apoptosis↗
PubMed2002

Eotaxin-2 generation is differentially regulated by lipopolysaccharide and IL-4 in monocytes and macrophages.

The eotaxins are a family of CC chemokines that coordinate the recruitment of inflammatory cells, in particular eosinophils, to sites of allergic inflammation. The cDNA for eotaxin-2 (CC chemokine ligand 24) was originally isolated from an activated monocyte library. In this study, we show for the first time that peripheral blood monocytes generate bioactive eotaxin-2 protein constitutively. Eotaxin-2 production was significantly up-regulated when monocytes were stimulated with the proinflammatory cytokine IL-1beta and the microbial stimuli, LPS and zymosan. In contrast, the Th2 cytokines, IL-4 and IL-13, and the proinflammatory cytokine, TNF-alpha, acting alone or in combination, did not enhance the generation of eotaxin-2 by monocytes. Indeed, IL-4 suppressed the generation of eotaxin-2 by LPS-stimulated monocytes. Although other chemokines, including macrophage-inflammatory protein-1alpha, monocyte chemoattractant protein-1, macrophage-derived chemokine, and IL-8 were generated by monocytes, eotaxin-1 (CC chemokine ligand 11) could not be detected in the supernatants of monocytes cultured in the presence or absence of any of the stimuli used in the above experiments. Furthermore, human dermal fibroblasts that produce eotaxin-1 did not generate eotaxin-2 under basal conditions or when stimulated with specific factors, including IL-4, IL-13, TNF-alpha, and LPS. When monocytes were differentiated into macrophages, their constitutive generation of eotaxin-2 was suppressed. Moreover, IL-4, but not LPS, up-regulated the production of eotaxin-2 by macrophages. Taken as a whole, these results support a role for macrophage-derived eotaxin-2 in adaptive immunity, with a Th2 bias. In contrast, a role for monocyte-derived eotaxin-2 is implicated in innate immunity.

Cells, Cultured↗
PubMed2002

Macrophage-colony-stimulating factor-induced activation of extracellular-regulated kinase involves phosphatidylinositol 3-kinase and reactive oxygen species in human monocytes.

We previously reported that activation of the phosphatidylinositol (PI) 3-kinase pathway was important in M-CSF-induced monocyte survival. Because M-CSF also induces activation of the mitogen-activated protein (MAP) kinase extracellular-regulated kinase (Erk), we focused on dissecting the mechanism used by M-CSF to induce Erk activation in human monocytes. We found that, in addition to the MAP/Erk kinase inhibitor PD098059, the PI 3-kinase inhibitors LY294002 and wortmannin both suppressed Erk activation in M-CSF-treated monocytes, suggesting that 3-phosphorylated products of PI 3-kinase played a role in Erk activation. Investigating the biochemical pathways regulated by PI 3-kinase to activate Erk, we found that, in response to M-CSF, normal human monocytes induced reactive oxygen species (ROS), which were suppressed by the PI 3-kinase inhibitor wortmannin but not by the solvent control DMSO or the MAP/Erk kinase inhibitor PD098059. We next found that, in the absence of M-CSF, ROS could induce Erk activation in human monocytes. Exogenous H(2)O(2) induced Erk activation in human monocytes, which was suppressed by exogenous catalase. To determine whether ROS induced by M-CSF played a role in Erk activation, we found that N-acetylcysteine and diphenyleneiodonium both suppressed Erk activation in M-CSF-treated monocytes. Erk activation by M-CSF also seemed to play a role in cellular survival in monocytes. These data suggest that, in M-CSF-stimulated human monocytes, PI 3-kinase products and ROS production play a role in Erk activation and monocyte survival.

Androstadienes↗
PubMed2002

Mycobacterium avium complex promotes recruitment of monocyte hosts for HIV-1 and bacteria.

In lymphoid tissues coinfected with Mycobacterium avium complex (MAC) and HIV-1, increased viral replication has been observed. This study investigates the role of MAC in perpetuating both infections through the recruitment of monocytes as potential new hosts for bacteria and HIV-1. Increased numbers of macrophages were present in the lymph nodes of patients with dual infection as compared with lymph nodes from HIV(+) patients with no known opportunistic pathogens. In a coculture system, monocyte-derived macrophages were treated with HIV-1 or M. avium and its constituents to further define the mechanism whereby MAC infection of macrophages initiates monocyte migration. Monocyte-derived macrophages treated with bacteria or bacterial products, but not HIV-1, induced a rapid 2- to 3-fold increase in recruitment of monocytes. Pretreatment of the monocytes with pertussis toxin inhibited the migration of these cells, indicating a G protein-linked pathway is necessary for induction of chemotaxis and thus suggesting the involvement of chemokines. Analysis of chemokine mRNA and protein levels from M. avium-treated cultures revealed MAC-induced increases in the expression of IL-8, macrophage-inflammatory protein (MIP)-1alpha, and MIP-1beta with donor-dependent changes in monocyte chemotactic protein-1. Pyrrolidine dithiocarbamate, an antioxidant, inhibited the activation of NF-kappaB and significantly diminished the MAC-induced chemotaxis, concurrently lowering the levels of monocyte chemotactic protein-1 and MIP-1beta. These data demonstrate that MAC induces macrophage production of multiple chemotactic factors via NF-kappaB to promote monocyte migration to sites of MAC infection. In vivo, opportunistic infection may act as a recruitment mechanism in which newly arrived monocytes serve as naive hosts for both MAC and HIV-1, thus perpetuating both infections.

Cell Movement↗
PubMed2005

Tumor cells deactivate human monocytes by up-regulating IL-1 receptor associated kinase-M expression via CD44 and TLR4.

Although blood monocytes possess significant cytotoxic activity against tumor cells, tumor-infiltrating monocytes are commonly deactivated in cancer patients. Monocytes pre-exposed to tumor cells show significantly decreased expression levels of TNF-alpha, IL-12p40, and IL-1R-associated kinase (IRAK)-1. Activation of the Ser/Thr kinase IRAK-1 is an important event in several inflammatory processes. By contrast, another IRAK family member, IRAK-M, negatively regulates this pathway, and is up-regulated in cultures of endotoxin-tolerant monocytes and in monocytes from septic patients within the timeframe of tolerance. In this study, we show that IRAK-M expression is enhanced at the mRNA and protein level in human monocytes cultured in the presence of tumor cells. IRAK-M was induced in monocytes upon coculturing with different tumor cells, as well as by fixed tumor cells and medium supplemented with the supernatant from tumor cell cultures. Moreover, blood monocytes from patients with chronic myeloid leukemia and patients with metastasis also overexpressed IRAK-M. Low concentrations of hyaluronan, a cell surface glycosaminoglycan released by tumor cells, also up-regulated IRAK-M. The induction of IRAK-M by hyaluronan and tumor cells was abolished by incubation with anti-CD44 or anti-TLR4 blocking Abs. Furthermore, down-regulation of IRAK-M expression by small interfering RNAs specific for IRAK-M reinstates both TNF-alpha mRNA expression and protein production in human monocytes re-exposed to a tumor cell line. Altogether, our findings indicate that deactivation of human monocytes in the presence of tumor cells involves IRAK-M up-regulation, and this effect appears to be mediated by hyaluronan through the engagement of CD44 and TLR4.

Adult↗
PubMed2006

The isoflavone genistein inhibits LPS-stimulated TNFalpha, but not IL-6 expression in monocytes from hemodialysis patients and healthy subjects.

BACKGROUND: Whole blood and peripheral blood mononuclear cells from hemodialysis (HD) patients show increased production and secretion of inflammatory cytokines. We determined the contribution of blood monocytes to the production of inflammatory cytokines in whole blood from HD patients. METHODS: Whole blood and isolated mononuclear cells from HD patients and healthy control subjects were preincubated with the isoflavone genistein and stimulated with LPS. TNFalpha, IL-6 and IL-10 formation in the whole blood was measured with ELISA and intracellular cytokine formation in CD 14-positive monocytes was determined by flow cytometry. RESULTS: Unstimulated blood levels of TNFalpha, IL-6 and IL-10 were significantly elevated in HD patients compared to controls, but intracellular monocyte content of these cytokines was identical between groups. LPS induced a robust TNFalpha response in both whole blood and monocytes, and TNFalpha formation was 2.3-fold higher in blood from HD patients compared to controls. A similar trend was observed in monocytes. Conversely, LPS stimulation increased IL-6 levels >1000-fold in whole blood, albeit without a noticeable difference between groups. Only minor increases in monocyte IL-6 content were observed. The isoflavone genistein did not inhibit IL-6 formation and did not alter basal TNFalpha levels, but genistein selectively blocked LPS-induced TNFalpha formation in whole blood and monocytes from both groups. CONCLUSION: Intracellular levels of TNFalpha, IL-6 and IL-10 in monocytes are indistinguishable between HD patients and healthy controls. However, monocytes from HD patients are selectively primed for enhanced TNFalpha secretion in response to LPS. The selective inhibition of monocyte TNFalpha production by genistein may explain the anti-inflammatory action of this phytochemical observed in vivo.

Adult↗
PubMed1999

CD40 ligand-activated human monocytes amplify glomerular inflammatory responses through soluble and cell-to-cell contact-dependent mechanisms.

Monocytes/macrophages play a critical role in the initiation and progression of a variety of glomerulonephritides. We sought to define the interactions between physiologically activated human monocytes and glomerular mesangial cells (MC) by employing a cell culture system that permits the accurate assessment of the contribution of soluble factors and cell-to-cell contact. Human peripheral blood monocytes, primed with IFN-gamma and GM-CSF, were activated with CD40 ligand (CD40L) or TNF-alpha and cocultured with MC. CD40L-activated monocytes induced higher levels of IL-6, monocyte chemoattractant protein-1 (MCP-1) and ICAM-1 synthesis by MC. Separation of CD40L-activated monocytes from MC by a porous membrane decreased the mesangial synthesis of IL-6 by 80% and ICAM-1 by 45%, but had no effect on MCP-1. Neutralizing Abs against the beta 2 integrins, LFA-1 and Mac-1, decreased IL-6 production by 40 and 50%, respectively. Ligation of mesangial surface ICAM-1 directly enhanced IL-6, but not MCP-1, production. Simultaneous neutralization of soluble TNF-alpha and IL-1 beta decreased MCP-1 production by 55% in membrane-separated cocultures of MC/CD40L-activated monocytes. Paraformaldehyde-fixed CD40L-activated monocytes (to preserve membrane integrity but prevent secretory activity), cocultured with MC at various ratios, induced IL-6, MCP-1, and ICAM-1 synthesis by MC. Plasma membrane preparations from activated monocytes also induced mesangial IL-6 and MCP-1 synthesis. The addition of plasma membrane enhanced TNF-alpha-induced mesangial IL-6 production by approximately 4-fold. Together, these data suggest that the CD40/CD40L is essential for optimal effector function of monocytes, that CD40L-activated monocytes stimulate MC through both soluble factors and cell-to-cell contact mediated pathways, and that both pathways are essential for maximum stimulation of MC.

CD18 Antigens↗
PubMed1999

Monocyte tissue factor expression is enhanced in women who smoke and use oral contraceptives.

The association between use of oral contraceptives (OCs) and increased risk of thromboembolic disease has been firmly established. This risk increases when use of OCs is combined with cigarette smoking. The cellular mechanism favoring an hypercoagulable state under these behaviours is not known. Circulating monocytes are potent activators of the coagulation cascade through their ability to synthesize procoagulant tissue factor (TF). In the present study we report that monocyte TF expression is increased in women who use OCs and smoke. We studied monocyte TF expression in 4 groups of healthy pre-menopausal women (n = 15 each): (1) non-smoking OC non-users, (2) nonsmoking current OC users, (3) smoking OC non-users and (4) smoking OC users. TF expression was assessed on both mRNA and protein levels in unstimulated and LPS-stimulated cells. Transcriptional activation of the TF gene was assessed by analysis of the transcription factor NF-kappaB and its inhibitor molecule IkappaBalpha. Monocyte TF generation was significantly higher in OC users than in women who did not use OCs. Enhanced monocyte TF generation was also observed in smoking women when compared to non-smokers. Strongest monocyte TF expression occurred in women with combined smoking and use of OCs. The enhanced TF expression in monocytes from women using OCs or smoking was based on an increased TF gene transcription following activation of NF-kappaB. Experiments on cultured monocytes/macrophages demonstrated enhanced IkappaBalpha degradation in the presence of estradiol, suggesting that a direct hormone effect is responsible for the observed increase in monocyte TF expression. This study demonstrates that use of OCs and smoking is associated with an increase in monocyte TF expression in pre-menopausal women. Aberrant TF expression by blood monocytes may favour intravascular clotting activation in women with OC therapy. The further enhancement of TF activity observed in women who smoke and use OCs may explain the synergistic effect of smoking on risk of thromboembolic events associated with contraceptive use.

Adolescent↗
PubMed2000

Lyprinol inhibits LTB4 production by human monocytes.

The effect of Lyprinol was evaluated on LTB4-induced human monocytes (normal and allergic donors) activation. Peripheral blood normal monocyte-derived monocytes when stimulated by Interleukin-4 (IL-4) produced high amounts of leukotriene B4 (LTB4) through the activation of the 5-lipoxygenase pathway. Maximal effect was observed in the presence of 10 ng/ml IL-4, and maximal LTB4 production was reached 40 min after the onset of stimulation. When stimulated for 48 h with IL-4, resting human monocytes expressed and released the low affinity receptor for IgE (CD23), and were inhibited in the presence of Lyprinol, or of the non redox 5-lipoxygenase inhibitor (BW B70C), suggesting that the production of LTB4 partially contributed to the IL-4-induced CD23 expression and release. In addition to these phenotypical changes, IL-4 primed the phorbol-12-myristate-13-acetate (PMA)-induced luminol-dependent chemiluminescence response (LDCL) by normal human monocytes; this priming effect was abrogated in the presence of Lyprinol, or of BW B70C. Monocyte-derived monocytes from allergic patients spontaneously produced high amounts of LTB4, expressed CD23 expression, and had an increased oxidative metabolism. In the presence of Lyprinol, or of BW B70C, the hyper-activation of monocytes from allergic patients was significantly suppressed. Taken together, these data indicated that the pharmacological control of the 5-lipoxygenase pathway in human monocytes can be achieved with Lyprinol, and that the activation of this pathway could upregulate the expression and release of CD23 and the respiratory burst of human monocytes.

Animals↗
PubMed2000

Monocyte tissue factor levels in cancer patients.

OBJECTIVE: The association between cancer and thromboembolic disease has been known for over a century. Increased tissue factor expression by endothelial cells, monocytes or macrophages is implicated. Thus, monocyte tissue factor measurements may reflect disease presence or progression. METHODS: Using a 2 stage kinetic chromogenic assay, monocyte tissue factor levels were assessed in normal controls (n=60), patient controls (hernia or cholecystectomy, n=60) and in patients with benign and malignant disease of the bladder (n=73), prostate (n=81), breast (n=83) and colorectum (n=62). This was performed as baseline (resting cells) and after 6 hours incubation with (stimulated) and without (unstimulated) lipopolysaccharide. Each benign disease group was sub-divided into inflammatory and non-inflammatory categories. RESULTS: The relative operating characteristic curve for the lipopolysaccharide-stimulated monocyte tissue factor assay showed sensitivity and specificity for cancer, the area under the curve being 0.71. The control groups and the benign non-inflammatory groups gave similar results and were pooled for further analysis. Each malignant group showed higher monocyte tissue factor levels than the control groups for baseline (P< 0.05) and lipopolysaccharide-stimulated cells (P< 0.05). All benign inflammatory groups apart from breast, showed increased monocyte tissue factor levels over controls for baseline (P< 0.05) and lipopolysaccharide-stimulated cells (P< 0.05). In all cases there was no significant difference between the malignant and the benign inflammatory groups. Monocyte tissue factor levels were related to tumor grade or stage, patients' survival time, serum prostate specific antigen and static bone scan images. Levels were also higher in patients with bladder cancer recurrence and in those who subsequently died. CONCLUSION: Lipopolysaccharide-stimulated monocyte tissue factor assay showed sensitivity and specificity for cancer compared to controls. Monocyte tissue factor levels are raised in malignant groups compared to controls and non-inflammatory diseases but not when compared with inflammatory conditions. Stimulated cells give better discrimination between the groups and may be useful in identifying high risk individuals. Monocyte tissue factor levels were related to tumor progression.

Adult↗
PubMed2002

Correlation between serum lipid profiles and the ratio and count of the CD16+ monocyte subset in peripheral blood of apparently healthy adults.

BACKGROUND AND PURPOSE: Deposited vascular oxidized low-density lipoproteins (LDLs) are important triggers of the transformation of circulatory monocytes into macrophages. CD16+ monocytes have been reported to be the precursors of tissue macrophages. In this study, we sought to determine the relationship between serum LDL-cholesterol and the percentage and count of the CD16+ monocyte subset in the peripheral blood of healthy adults. METHODS: We studied the correlations between serum lipid profiles and both peripheral CD16+ and CD36+ monocyte subset ratios and counts in apparently healthy adults (50 men and 50 women). Monocyte surface antigens CD16 and CD36 on CD14+ monocytes were detected using fluorescent triple staining and flow-cytometry. Surface staining was performed by incubating 1 x 10(6) blood mononuclear cells with phycocrythrin-conjugated anti-CD14, fluorescein isothiocyanate-conjugated anti-CD36, and respective control isotopes (mouse IgGs). A total of 5,000 cells were counted and the frequency of surface antigens was determined by FACscan. RESULTS: A significant positive link between LDL-cholesterol and the CD16+ subset ratio was found by linear correlation analysis (p < 0.05) but not by multivariate regression analysis. Both linear correlation analysis and ANOVA revealed a significant inverse link between high-density lipoprotein (HDL)-cholesterol and the CD16+ subset ratio (both p < 0.01). By multivariate regression analysis, gender was the main significant determinant for the CD16+ subset ratio. When serum total cholesterol (TC) was excluded from the analysis to avoid the interference from collinearity between serum TC and LDL (r = 0.84), HDL-cholesterol became independently and inversely linked to the CD16+ subset ratio. There were independent inverse links between HDL-cholesterol and the counts of all monocytes, CD16+ monocytes, and CD36+ monocytes. CONCLUSIONS: Our results suggest that circulating HDL-cholesterol may be much more important than LDL-cholesterol in affecting the transformation of circulatory monocytes into macrophages. The inverse link between HDL-cholesterol and the number of macrophage precursors in peripheral blood might contribute partly to the well-known antiatherogenic effect of HDL-cholesterol.

CD36 Antigens↗
PubMed2002

Modulation of monocyte signaling and pore formation in response to agonists of the nucleotide receptor P2X(7).

Previous reports about the nucleotide receptor P2X(7), which exhibits ion channel and pore-forming activity and is known to promote IL-1beta processing, have centered largely on its role in macrophage function, whereas its participation in monocyte activity has been unclear. However, because extracellular ATP has been shown to affect monocytes with respect to IL-1beta release, we hypothesized that the P2X(7) receptor is also present and functional in a subpopulation of blood monocytes. Flow cytometric analysis revealed that about 70% of monocytes isolated from normal human donors expressed the P2X(7) receptor. Activation of P2X(7) receptor-associated pore formation by the agonist BzATP resulted in a 9- to 15-fold increase in the uptake of the membrane-impermeant fluorescent dye YO-PRO, and this dye uptake is markedly inhibited by the P2X(7) receptor antagonists KN-62 and oATP. Evidence supporting the presence of the functional P2X(7) receptor in monocytes also includes the observation that BzATP exposure results in a dose-dependent increase in the activation of mitogen-activated 2protein kinases and the nuclear translocation of the transcription factor NF-kappaB in human monocytes and in THP-1 human monocytic cells. Furthermore, treatment of monocytes with BzATP induced the expression of cyclooxygenase-2 (COX-2) and tissue factor, which are two important endpoints that have not been previously shown to be regulated by nucleotide receptor action in monocytes. Together, these data indicate that a subpopulation of human monocytes express P2X(7) receptors that are functional with respect to pore formation, signal transduction, and mediator production, further supporting a key role for this nucleotide receptor in host immune responses.

Benzoxazoles↗
PubMed1992

Heterogeneity of human blood monocyte: two subpopulations with different sizes, phenotypes and functions.

Human blood mononuclear cells from normal adults were collected after density-cut centrifugation and monocytes were then isolated by removal of lymphocytes using the techniques of E-rosetting and cell adhesion. The purified monocytes were further analysed by velocity sedimentation, and two distinct subpopulations with different cell sizes were obtained. The larger monocytes were 17.0 +/- 1.8 microns in diameter with a mean sedimentation rate (SR) of 7.0 +/- 0.6 mm/hr, while the smaller monocytes were 9.5 +/- 0.8 microns in size and 4.1 +/- 0.2 mm/hr in SR. The population ratio of larger:smaller cells was approximately 2:1 (66 +/- 2.8%:34 +/- 1.6%). Both cell populations exhibited a high positive rate (> 98%) in both the non-specific esterase and the peroxidase stain. However, the larger cells had much higher phagocytic activity than the smaller ones. Furthermore, the expression of monocyte-associated antigens was also different between these two subpopulations. Thus, while most of the larger monocytes (98%) could be recognized by monoclonal antibodies MY7 and OKM1, only some (35 and 61%, respectively) of the smaller monocytes could react with those antibodies. In addition, the larger monocytes secreted a significant amount of monokines including interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2) and their production increased in proportion to the level of stimulation by bacterial lipopolysaccharide (LPS), whereas the production of monokines by the smaller monocytes remained at low levels and did not respond to LPS stimulation. These results reveal the existence of phenotypic and functional heterogeneity in human blood monocytes.

Adult↗
PubMed2004

[Changes in human leukocyte antigen-DR expression on monocytes and its value of prediction on infection complication in trauma patients].

OBJECTIVE: To observe the changes of human leukocyte antigen DR (HLA-DR) expression in monocytes of trauma patients and its value of prediction on infection complications. METHODS: Fifty-four trauma patients were divided into three groups according to severity of injury: severe trauma group injury severity score (ISS) >or=25, moderate trauma group (16 or=16) were divided into three groups according to infection or not: no infection group, localized infection group and systemic infection group. Blood samples were collected immediately after admission and serially at 8:30 to 9:00 a.m. on days 1, 2, 4, 6, 8, 14 after admission, and monocyte HLA-DR expression was determined with monoclonal staining and flow cytometry. RESULTS: The HLA-DR expression in monocytes was reduced in the trauma patients. The lowest levels of HLA-DR were recorded on day 2 after trauma. Subsequently HLA-DR expression in monocytes increased gradually. During the whole observation, the HLA-DR expression was significantly decreased in both severe trauma group and moderate trauma group versus control group, but no significant differences were found between severe trauma group and moderate trauma group, mild trauma group and control group, Immediately after trauma, HLA-DR expression in monocytes was significantly lower in the localized infection group than that in the patients without infection, and lasted until day 4 after trauma. The mean fluorescence intensity of HLA-DR expression in monocytes on the day 2 to 14 after trauma, the percentage of HLA-DR monocytes on the day 1 to 14 after trauma were significantly lower in the systemic infection group than those in the localized infection group. The level of HLA-DR expression in monocyte in the 2 died trauma patients was lowered till died. CONCLUSION: In severe trauma patients, the HLA-DR expression in monocytes is significantly decreased, and decreased levels of HLA-DR expression in monocytes might be the early indicators of an immune deviation associated with the development of infection complications and prognosis.

Adult↗