Protein Kinase C alpha Regulates the Expression of Complement Receptor Ig in Human Monocyte-Derived Macrophages

摘要

The complement receptor Ig (CRIg) is selectively expressed by macrophages. This receptor not only promotes the rapid phagocytosis of bacteria by macrophages but also has anti-inflammatory and immunosuppressive functions. Previous findings have suggested that protein kinase C (PKC) may be involved in the regulation of CRIg expression in human macrophages. We have now examined the role of PKC alpha in CRIg expression in human monocyte-derived macrophages (MDM). Macrophages nucleofected with plasmid containing short hairpin RNA against PKC alpha showed markedly reduced expression of PKC alpha, but normal PKC zeta expression, by Western blotting analysis, and vice versa. PKC alpha-deficient MDM showed increased expression of CRIg mRNA and protein (both the long and short form), an increase in phagocytosis of complement-opsonized Candida albicans, and decreased production of TNF-alpha and IL-6. TNF-alpha caused a marked decrease in CRIg expression, and addition of anti-TNF mAb to the TNF alpha-producing MDMs increased CRIg expression. PKC alpha-deficient macrophages also showed significantly less bacterial LPS-induced downregulation of CRIg. In contrast, cells deficient in PKC alpha showed decreased expression of CR type 3 (CR3) and decreased production of TNF-alpha and IL-6 in response to LPS. MDM developed under conditions that increased expression of CRIg over CR3 showed significantly reduced production of TNF-alpha in response to opsonized Candida albicans. The findings indicate that PKC alpha promotes the downregulation of CRIg and upregulation of CR3 expression and TNF-alpha and IL-6 production, a mechanism that may promote inflammation.