Regulation of phagocytic leukocyte activities by C-reactive protein

The classic acute phase reactant C-reactive protein (CRP) is classified as an effector of innate host resistance because it activates die classical complement cascade and is opsonic, The latter action occurs via specific CRP receptors (CRP-R) that have recently been identified as both Fc gamma RI and Fc gamma RII on human phagocytic leukocytes, New findings also suggest an anti-inflammatory role for CRP because it modulates endotoxin shock and inhibits chemotaxis and the respiratory burst of neutrophils, CRP inhibited phorbol myristate acetate-induced superoxide (O-2(-)) production more efficiently than the fMLP-triggered response, An examination of the inhibition of the protein kinase C (PKC)-dependent assembly of the NADPH oxidase complex revealed that both phosphorylation and translocation of PKC-beta 2 to the membrane were inhibited by a threshold acute phase dose of similar to 50 mu g/mL CRP. Translocation to the membrane and serine-phosphorylation of the major cytosolic p47-phox component of the NADPH oxidase complex was inhibited by CRP, CRP also inhibited membrane localization of activated Rac2, the small G protein regulator of the assembly of the oxidase components in activated neutrophils as well as the cytoskeleton during chemotactic movement, CRP-mediated regulation occurs via the CRP-R because an IgM mouse mAb to the human CRP-R mimicked CRP-induced inhibition of O-2(-) production and chemotaxis. CRP may serve as an anti-inflammatory regulator of activities at sites of tissue damage where it selectively accumulates and thus influences neutrophil infiltration and polymorphonuclear neutrophil activities, By contrast, CRP activates cells of the monocyte/macrophage lineage, suggesting differential regulation of these two leukocyte populations at the level of signaling, CRP appears to be a multifunctional protein with the capability of exerting both effector functions for innate host resistance, as well as exerting specific anti-inflammatory effects.