The project is directed to defining the role of phospholipases in eosinophil leukocytes activity with regard to formation of mediators of inflammation and the host response to helminthic infections.
The specific aims i nclude the demonstration and biochemical characterization of the phospholipases (A & B) of the eosinophils focusing on their quantitative relation in the cells and on the factors (co-lipase, substrate form) conditioning their sequential activity in intact cells and solubilized and fractionated preparations. A second line of inquiry aims to establish the extent and significance of the phospholipase-mediated reactions in the incorporation, distribution and mobilization of the arachidonic acid of the cell phospholipids before and during challenge of the eosinophils with specific stimuli known to induce secretion of cellular components and the expression of the cytotoxic action of the cells against parasites.
The third aim i s to assess participation of the phospholipases and products of their activity in the cytotoxic effects on helminthic parasites (Trichinella spiralis larvae) exposed in vitro to eosinophils in the presence of activating factors (complement, antibodies, ECFA). The extracellular release of the enzymes and their adhesion and effects on the parasite bodies will be studied together with analytical estimates of the production and accumulation of intermediate metabolites (lysophospholipids, GPC, GPE) and precursors of compounds of the prostaglandin, thromboxane and hydroxyfatty acid group.
| Ottolenghi, Athos; Rowland, John T (2002) Phospholipase and lysophospholipase activity of rat eosinophil leukocytes. Arch Biochem Biophys 406:190-202 |
