During the acute phase of an inflammatory process, a number of changes occur in the cellular and plasma compartments of the blood. These humoral and cellular components of the acute phase response have been independently characterized; however, few studies have focused on the interaction of acute phase proteins with blood leukocytes. Our laboratory has reported that C-reactive protein (CRP), an acute phase reactant, binds to human monocytes and neutrophils and enhances their respiratory burst response to IgG. The proposed studies are designed to examine the specificity of this effect by determining whether CRP modulates monocyte and neutrophil chemiluminescence and superoxide anion generation following stimulation with phorbol myristate acetate, serum-opsonized zymosan, N-formyl-methionyl-leucyl-phenylalanine, or A23187. Lysosomal enzyme release induced by those stimuli will also be measured to establish whether CRP can similarly modify secretory processes in human phagocytic cells. To gain more information concerning the mechanism of the CRP enhancement of IgG-induced respiratory burst activity, the proposed studies will examine whether CRP and IgG interact with human phagocytic cells at discrete or related membrane sites. These binding reactivities will be discriminated by examining the topographical distribution of surface-bound fluorescent-labeled IgG and CRP. Further information concerning the mechanism of CRP enhancement and the relationship between the IgG Fc receptor and the CRP binding site will be obtained from studies measuring CRP and IgG induced whole cell currents in monocytes and neutrophils. Currents generated by IgG, CRP and a combination of these proteins will be characterized and compared. The process of specific receptor desensitization following repeated exposure to a given stimulus will be used to determine whether CRP binds to monocytes and neutrophils at the same site as IgG. The results of these studies will further clarify the nature of the interaction between CRP and human phagocytic cells during episodes of acute inflammation. Furthermore, they will serve as the foundation for future studies that will examine and more completely characterize the nature of the putative CRP receptor on human moncytes and neutrophils.
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