A role for CD21/CD35 and CD19 in responses to acute septic peritonitis: A potential mechanism for mast cell activation

Although it is now appreciated that mast cell-mediated release of TNF-alpha is critical for resolution of acute septic peritonitis, questions remain a s to how mast cells are activated upon peritoneal bacterial infection, Clue s to how this may occur have been derived from earlier studies by Prodeus e t al, in which complement proteins C3 and C4 were shown to be required for survival following cecal ligation and puncture (CLP), a model for acute sep tic peritonitis, To evaluate the mechanism for mast cell activation in the CLP model, complement receptor CD21/CD35-deficient mice (Cr2(null)) were ex amined in the present study, Along with CD19-deficient (CD19(null)) mice, t hese animals exhibit decreased survival Following CLP compared with wild-ty pe littermates. Injection of IgM before CEP does not change survival rates for Cr2(null) mice and only partially improves survival of CD19(null) mice, implicating CD21/CD35 and CD19 in mast cell activation. Interestingly,earl y TNF-alpha release is also impaired in Cr2(null) and CD19(null) animals, s uggesting that these molecules directly affect mast cell activation. Cr2(nu ll) and CD19(null) mice demonstrate an impairment in neutrophil recruitment and a corresponding increase in bacterial load, Examination of peritoneal mast cells by flow cytometry and confocal microscopy reveals the expression and colocalization of CD21/CD35 and CD19, Taken together, these findings s uggest that the engagement of complement receptors CD21/CD35 along with CD1 9 on the mast cell surface by C3 fragments may be necessary for the full ex pression of mast cell activation in the CLP model.