Serum of Patients with Behçet’s Disease Induces Classical (Pro-Inflammatory) Activation of Human Macrophages in vitro

Abstract

Background: Although several immunological abnormalities have been demonstrated in Behçet’s disease (BD), the exact mechanism of the inflammatory changes occurring is still unknown. Antigen-presenting cells, such as mononuclear phagocytes, play a major role in the regulation of immune-mediated as well as of non-specific inflammation. Objective: To investigate the serum activity of patients with BD on antigen and chemokine expression of human macrophages in vitro. Methods: Serum of 15 patients (8 women, 7 men; mean age 33 ± 10 years) with BD was incubated with cultured macrophages isolated from peripheral blood of healthy volunteers. Macrophages maintained in patients’ serum, fetal calf serum with/without dexamethasone and interleukin (IL)-4 or γ-interferon were investigated for alternative macrophage-activation-associated CC-chemokine 1 (AMAC-1) and IL-8 mRNA expression by Northern blotting. In addition, cytocentrifuge macrophage preparations were stained with monoclonal antibodies against proteins indicating alternative (anti-inflammatory) macrophage activation, such as MS-1 high-molecular-weight protein (MS-1-HMWP), RM3/1 antigen (CD163) and 25F9, as well as classical (pro-inflammatory) macrophage activation, such as CD11c, class I receptor binding the Fc part of IgG (FcγRI: CD64) and class III receptor binding the Fc part of IgG (FcγRIII: CD16). Results: Macrophages treated with patients’ serum showed neither AMAC-1 expression nor staining with monoclonal antibodies for MS-1-HMWP, CD163 or 25F9. Concomitant treatment with IL-4/dexamethasone up-regulated significantly the expression of CD163. In contrast, IL-8 mRNA expression and staining for CD11c and CD64 were strongly positive after treatment with serum of patients with BD. CD64 positivity and IL-8 mRNA expression were more prominent in patients with active BD than in patients with inactive disease. Conclusion: Taken together, our results indicate that serum of patients with BD induces classical (pro-inflammatory) activation of human peripheral blood macrophages in vitro. Our findings suggest that serum factor(s) may be responsible for inflammatory changes in BD.

The natural course and factors affecting severity of Behçet’s disease: a single-center cohort of 368 patients

“…Behçet's disease (BD) is a chronic, relapsing inflammatory process causing various mucocutaneous, ocular, articular, vascular, gastrointestinal, urogenital, pulmonary, neurological symptoms and signs [1]. The onset symptom, chronological order of subsequent symptoms and the duration among these symptoms vary from one patient to another.…”

Oxidases and oxygenases in regulation of neutrophil redox pathways in Behçet’s disease patients

“…The high-affinity Fc receptor (FcgR1/CD64) is considered a marker of PMN activation and is strongly positive in BD patients, especially in patients with active BD than in patients with inactive disease 7 . Another sensitive marker of neutrophil activation is decreased surface expression of L-selectin (CD62L), which is shed upon PMN stimulation via proteolytic cleavage 8 .…”

Androgen Receptor Levels of Oral and Genital Ulcers and Skin Pathergy Test in Patients with Behçet’s Disease

“…The aetiopathogenesis of the disease still remains unknown, although several factors have been accused [1, 2]. Hormonal factors have long been proposed to play a role in BD.…”