Submitted to: Veterinary Immunology International Symposium
Publication Type: Abstract Only
Publication Acceptance Date: 7/15/2001
Publication Date: N/A
Technical Abstract: Fc receptors of avian heterophils play a primary role in the elimination of bacterial pathogens in poultry. The cross-linking of Fc receptors with bacteria-Ig complexes results in the secretion of toxic oxygen metabolites and anti-bacterial granules. We have been investigating the upstream signaling events that precede degranulation by heterophils. Using the non-specific pharmacological inhibitors genistein, chelerythrine, and staurosporin, we found no significant inhibitory effects on Fc-mediated heterophil degranulation. In these studies, we used more selective pharmacological inhibitors to investigate the roles of mitogen activated protein kinases, tyrosine kinases, phospholipases, phosphatidylinositol 3'-kinase, and intracellular calcium mobilization on Fc-mediated heterophil degranulation. Neither PP2, a selective inhibitor of the Src family of protein tyrosine kinases, nor piceatannol, a selective inhibitor of Syk tyrosine kinase, had inhibitory effects on degranulation. However, Fc-mediated degranulation was significantly attenuated by SB 203580, an inhibitor of p38 MAPK, U73122, an inhibitor of phospholipase C, and LY294002, an inhibitor of PI3-kinase. Lastly, chelation of extracellular calcium by EGTA did not affect degranulation whereas chelation of intracellular calcium by BAPTA attenuated this response. These results suggest that p38 MAPK, phospholipase C, PI3-K, and calcium mobilization participate in the signaling pathways that regulate Fc-receptor-mediated degranulation of chicken heterophils.