This subproject investigates the consequences of crosslinking receptors for the Fc portion of immunoglobulin G (Fcgamma) and for fragments of the third component of complement on the function of human polymorphonuclear leukocytes (PMN). We have previously shown that crosslinking the 40 kilodalton FcgammaRII receptor activates the PMN as assessed by lysosomal enzyme release and the generation of superoxide, and that these responses are partially inhibited by pertussis toxin. Mobilization of calcium ions (Ca2+), also triggered by FcRII crosslinking, is not inhibited by pertussis toxin. We now propose to study the mechanisms involved in the transduction of this signal, including phosphatidylinositol metabolism, protein kinase C activation, guanine nucleotide binding proteins and protein phosphorylation. Interactions of FcgammaRII with other PMN receptors such as FcgammaIII, complement receptors 1 and 3, beta glucan, mannosyl/fucosyl, C5a, formyl-peptide and fibronectin will also be examined in terms of their capacity to synergize or antagonize signalling for PMN activation. Finally, factors which influence the metabolism and expression of FcgammaRII on the cell surface will be studied. Preliminary data indicating that the receptor is rapidly internalized will be further explored, and the factors which influence cycling of the receptors will be determined. Alterations in protein synthesis triggered by receptor signalling will be examined. The goal of the subproject is increased knowledge of the functioning of Fc and complement receptors on PMN and the cell processes these receptors govern.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298