PHYSIOPATHOLOGY OF THE INFLAMMATORY REACTION

Neutrophils are thought to be responsible for the inflammatory reaction in gout and rheumatoid arthritis. We are currently studying the phospholipase D (PLD) family of proteins. PLD enzymes are involved in the regulation of intracellular membrane traffic and in the control of important neutrophil functions such as secretion and phagocytosis. Our research aims at defining the functions of the PLD isoforms and determining their mechanisms of activation.

Our first objective is to determine the effects of mutant GTPases (Arf and RhoA) and nucleotide exchangers (ARNO and cytohesine-1) on PLD activity in cells. We are examining the expression and the subcellular distribution of the PLD isoforms.

Our second objective is to characterize the cell surface receptors Fc and CD11b and to determine the PLD isoform activated by monosodium urate crystals. Finally, our last study aims at understanding the molecular mechanisms by which prostaglandin E2 and adenosine inhibit PLD activity in neutrophils.We hope to exploit these proteins’ properties to reduce joint tissue damage in arthritis.

These projects are supported by the Medical Research Council of Canada, the Fonds de la recherche en santé du Québec and the Arthritis Society of Canada.

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