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Background Systemic lupus erythematosus (SLE) is characterized by increased cardiovascular morbidity and mortality. SLE patients have increased prevalence of subclinical atherosclerosis, although the mechanisms of this observation remain unclear. Considering the emerging role of monocytes in atherosclerosis, we aimed to investigate the relationship between subclinical atherosclerosis, endothelial dysfunction and the phenotype of peripheral blood monocytes in SLE patients. Methods We characterized the phenotype of monocyte subsets defined by the expression of CD14 and CD16 in 42 patients with SLE and 42 non-SLE controls. Using ultrasonography, intima-media thickness (IMT) of carotid arteries and brachial artery flow-mediated dilation (FMD) as well as nitroglycerin-induced dilation (NMD) were assessed. Results Patients with SLE had significantly, but only modestly, increased IMT when compared with non-SLE controls (median (25th/75th percentile) 0.65 (0.60/0.71) mm vs 0.60 (0.56/0.68) mm; p < 0.05). Importantly, in spite of early atherosclerotic complications in the studied SLE group, marked endothelial dysfunction was observed. CD14dimCD16+proinflammatory cell subpopulation was positively correlated with IMT in SLE patients. This phenomenon was not observed in control individuals. Interestingly, endothelial dysfunction assessed by FMD was not correlated with any of the studied monocyte subsets. Conclusions Our observations suggest that CD14dimCD16+monocytes are associated with subclinical atherosclerosis in SLE, although the mechanism appears to be independent of endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Based on CD14 and CD16 expression, human peripheral blood monocytes (MO) can be divided into a major CD14high CD16− population and two minor CD14high CD16+ and CD14dim CD16+ subpopulations. CD14dim CD16+ MO are well characterized and regarded as pro-inflammatory because upon stimulation produce TNF-α but little, if any, IL-10. By contrast, little is known about CD14high CD16+ MO. We investigated the surface expression of selected determinants by CD16+ MO subpopulations, cytokine production, phagocytosis and antigen presentation. We found that both CD16+ subpopulations had a higher expression of HLA-DR, CD86, CD54 and a lower expression of CD64 than CD14high CD16− population. In addition, CD14high CD16+ MO showed a higher expression of CD11b and TLR4 than CD14dim CD16+ and CD14high CD16− subpopulations. CD14high CD16+ MO exhibited an increased phagocytic activity and a decreased antigen presentation in comparison with CD14dim CD16+. As expected, lipopolysaccharide (LPS)-stimulated CD14dim CD16+ MO produced TNF-α but little IL-10. By contrast, LPS-stimulated CD14high CD16+ subpopulation produced significantly more IL-10 than CD14dim CD16+ and CD14high CD16− MO. In conclusion, our data show that human peripheral blood CD16+ MO are heterogeneous in function and consist of two subpopulations: CD14dim CD16+ pro-inflammatory and CD14high CD16+ with anti-inflammatory potential. [ABSTRACT FROM AUTHOR]

Staphylococcus aureushas important implications for the pathogenesis of atopic dermatitis (AD). In some patientsS. aureuscan be eradicated from the skin during anti-inflammatory treatment, while in others bacterial colonization is persistent. Potential mechanisms and features of these two distinct groups of patients are not known.Accordingly, we studied relationships between the ability to eliminateS. aureusduring an anti-inflammatory treatment and selected clinical and immunological features.Quantitative assessment ofS. aureuson the skin, in nasal vestibule and throat, serum IgE levels, CD4/CD8 T-cell ratio, lymphocyte proliferation and phagocyte oxidative burst were determined during the exacerbation and after 4 and 12 weeks of the treatment using topical steroid and oral antihistamine in 34 patients with AD.S. aureuswas found on the skin of all 34 patients during exacerbation. Disease severity scoring of atopic dermatitis (SCORAD) correlated with the density of bacteria. Treatment with oral antihistamine and topical steroid resulted in a significant alleviation of symptoms, which correlated with the elimination ofS. aureusfrom the skin in 70% of patients. In the remaining 30% of patients, dense (more than 1010/cm2)S. aureusskin colonization, persisted despite the treatment. Patients with persistentS. aureuspresented with higher serum IgE levels, lower lymphocyte proliferation in response to staphylococcal enterotoxin B, phytohaemagluttinin and anti-CD3. Persistence ofS. aureuswas more common in men.Patients with AD differ in the ability to clearS. aureusfrom the skin during anti-inflammatory treatment, which appears to be related to the abnormalities in immunological parameters. Local antibiotic therapy should be considered only in patients with persistentS. aureuscolonization. [ABSTRACT FROM AUTHOR]

The phenotype and function of peripheral blood monocytes change after trauma and during sepsis. The aim of the study was to evaluate monocyte expression of human leucocyte antigen (HLA)-DR and Fc receptor III (FcR III) (CD16) in neonates and small children with high risk of sepsis (hospitalized at the intensive care unit). The reduced proportion of CD14+ HLA-DR+ monocytes was observed in all patients at the intensive care unit, while the increase of CD16 expression on monocytes was observed in the course of sepsis. The measurement of CD16 expression on monocytes also proved to be more useful for monitoring patient. The proportion of both CD14dim CD16+ and CD14high CD16+ monocytes increased during sepsis; however, monocytes showed reduced ability to phagocytose Escherichia coli , compromised ability to cooperate with T cells and reduced CD86 expression in parallel to HLA-DR depression. The reduced interleukin (IL)-1 but rather increased IL-10 production was associated with sepsis. The differences between CD14+ CD16+ monocytes of healthy donors and patients with sepsis are discussed. [ABSTRACT FROM AUTHOR]

Monocyte subpopulations which differ in the expression of Ec receptor for human IgO (FcRI) differentially regulate the T-cell-dependent, pokeweed mitogen (PWM)-induced, polyclonal B-cell response. We, thus, studied the cytokine production in human peripheral blood monocyte and T-Iymphocytc cultures activated with this lectin. Monocytes or their FcR+ and FcR subpopulations stimulated with PWM were cultured with or without T lymphocytes or their CD4+ and CD8+ subsets. Both monocyte subpopulations cultured alone produced similar amounts of tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), but FcR monocytes showed significantly enhanced ability to secrete interleukinel (IL-1). T cells, especially CD44 ,added to monocyte cultures enhanced IL-1 production. This enhancement was presumably due to interferon-gamma (IFN-γ) release by T lymphocytes. since this lymphokine enhanced IL- 1 secretion when added to PWM-stimulated cultures of monocytes. Addition of monocytes. in particular the FcR+ subpopulation, greatly enhanced production of IEN-γ by T lymphocytes. Although both 1-cell subsets produced IEN-γ, the CD4+ cells were more efficient. These results indicate that in PWM-stimulated cultures subpopulations of monocytes differ in secretion of cytokines, which might explain their differential effect on T-cell-dependent immune responses in vitro. [ABSTRACT FROM AUTHOR]

Monocyte-T-cell interactions were studied in pokeweed mitogen (PWM)-activated cell cultures. We addressed the question of monocyte changes in PWM-stimulated cultures of T cells and monocytes and found, by flow cytometric analysis, that PWM activation led to a loss of cells with monocyte or macrophage phenotype (CD14, HLA-DR, HLA-DQ) within 48 hr of culture in the presence of T cells (CD4+ T cells), but not in cultures of pure monocytes. Chemiluminescence measurements revealed that phagocytic stimulation of monocytic superoxide release was impaired in PWM-stimulated cultures of monocytes plus T cells, but not in PWM-stimulated cultures of pure monocytes. Furthermore, PWM induced the secretion of interferon-gamma (IFN-γ) in primary cultures oft cells supplemented with 20% of monocytes, whereas in subsequent secondary cultures of these cells PWM induced IFN-γ only when monocytes were added. We conclude from these flow cytometric and functional analyses that monocytes are efficiently eliminated from PWM-activated T-cell/monocyte cultures by CD4+ T lymphocytes. [ABSTRACT FROM AUTHOR]

The number of immunoglobulin-secreting cells (ISC) upon stimulation with pokeweed mitogen (PWM) or Staphylococcus aureus Cowan I (SAC) in recombinant interleukin-2 (rIL-2)-supplemented cultures of human peripheral blood mononuclear cells (PBMC) and co-cultures of B and T cells was studied. It has been shown that the addition of rIL-2 to culture can enhance or depress the number of ISC depending on the polyclonal B-cell activator used for culture stimulation. The SAC-induced response was enhanced in the presence of rIL-2, while the number of LSC in PWM-stimulated cultures was depressed. Moreover, in cultures stimulated simultaneously by both activators, the suppressive effect of rIL-2 prevailed, indicating that the reported direct effect of the lymphokine on SAC-activated B cells cannot overcome the suppressive activity of PWM-induced suppressor T cells. rIL-2 could not activate suppressor T cells in the absence of PWM, and has no effect on the number of helper or suppressor cells in the culture. [ABSTRACT FROM AUTHOR]

In co-cultures with control cells lymphocytes obtained from some patients with hypogammaglobulinaemia can suppress PWM but not S. aureus Cowan I-induced polyclonal immunoglobulin production. When such co-cultures were stimulated at the same time with both mitogens, the response was greatly suppressed. This phenomenon was further studied in cultures of lymphocyte populations isolated from healthy donors. It was found that suppressor T lymphocytes activated by PWM in cultures (1 )co-stimulated with Con A, (2) with high T: B cell ratio, or (3) with an increased proportion of OKT8+ T cells can suppress the S. aureus-induced response. In contrast, under the same conditions S. aureus did not activate suppressor cells. Moreover, in cultures stimulated with this polyclonal B-cell activator 0KT8+ lymphocytes could serve as helper cells. [ABSTRACT FROM AUTHOR]

Human peripheral blood monocyte subsets with and without Fc receptor for human IgG are known to suppress (FcR+) and enhance (FcR) pokeweed mitogen-induced polyclonal immunoglobulin synthesis in vitro. The ability of these subsets to modulate immunoglobulin production in the presence or absence oF OKT8+ T cells and under conditions where suppressor T-cell activation was blocked by irradiation or mitomycin C was studied. It was shown that, regardless of the presence or absence of suppressor T cells. FcR+ monocytes can suppress immunoglobulin production if their number in culture exceeds 20%. However, at lower numbers this monocyte subset was suppressive only when suppressor T cells were activated. The suppressor T-cell activation was shown to be independent of the predominant presence of the FcR+ or FcR monocyte subset. Moreover, the enhancing effect of FcR monocytes was not caused by their interference with suppressor T-cell activation. [ABSTRACT FROM AUTHOR]

Supernatants from 18-hr cultures of human peripheral blood polymorphonuclear cells (PMN) and adherent cells (AC) inhibited the binding of erythrocyte-antibody complexes (EA) by PMN. The inhibitory activity was lost upon absorption on lgG and Fc, but not on the F(ab')2 fragment of IgG. IgG-binding material (shed Fc receptor-FcR) was reutilized by PMN and AC which had lost their own FcR in vitro. Reutilization was independent of the type of cells from which FcR originated. The FcR-containing material eluted from IgO-coated Sepharose column inhibited PH A -induced Lym phoproliferation, probably via prior interaction with monocytes. These results suggest that shed FcR may be freely exchanged between different types of human leucocytes and play a role in the suppression of mitogen-induced T-cell responses. [ABSTRACT FROM AUTHOR]