Sequential Increase in Complement Factor I, iC3b, and Cells Expressing CD11b or CD14 in Cutaneous Vasculitis

Area of Science:

• Immunology
• Dermatology
• Pathogenesis of Vasculitis

Background:

• Mast cells play a role in cutaneous vasculitis pathogenesis.
• The complement cascade involves C3 cleavage to C3b and iC3b.
• Receptors for iC3b, CD11b and CD14, are present on immune cells, but their role in vasculitis is unclear.

Purpose of the Study:

• To investigate the expression and role of complement factor I, iC3b, CD11b, and CD14 in immunocomplex-mediated small vessel vasculitis.
• To examine the relationship between mast cell C3c, iC3b, and CD11b/CD14 expressing cells.
• To assess the functional impact of iC3b and C3a on immune cell migration and cytokine secretion.

Main Methods:

• Immunohistochemical analysis of skin biopsies from patients with vasculitis (nonlesional, early, and advanced lesions).
• Analysis of peripheral blood mononuclear cells from healthy subjects.
• Transwell migration assays and cytokine secretion studies (interleukin-8).

Main Results:

• Complement factor I, iC3b, CD11b, and CD14 were expressed in nonlesional skin and increased in active vasculitis lesions.
• Mast cell C3c correlated with iC3b, which in turn correlated with CD11b+ and CD14+ cells.
• iC3b induced mononuclear cell migration, while C3a and iC3b had minor effects on interleukin-8 secretion.

Conclusions:

• The C3-C3b-iC3b complement axis is activated early in vasculitis.
• This activation leads to the progressive accumulation of CD11b+ and CD14+ cells in the affected skin.
• These findings highlight a potential mechanism in the pathogenesis of cutaneous vasculitis.