Induction of Secretory Phospholipase A.sub.2 Confirms the Systemic Inflammatory Nature of Adjuvant Arthritis

Byline: Manfred Koo Seen Lin (1), Alan Katz (2), Henk Van Den Bosch (3), Brian Kennedy (4), Eva Stefanski (1), Peter Vadas (1), Waldemar Pruzanski (1) Abstract: Adjuvant arthritis (AA) is an accepted model of inflammatory arthritis. Until now, however, there is little information about inflammatory mediators, specifically in relation to the arachidonic acid cascade in AA. Our objective was to study the expression of secretory (sPLA.sub.2) and cytosolic (cPLA.sub.2) phospholipases A.sub.2 in various organs during the course of AA. AA was induced in Lewis rats which were sacrificed at days 0, 7, 14, 21, 28 and 42. Expression of sPLA.sub.2 mRNA and protein and mRNA of cPLA.sub.2 in paws, regional lymph nodes, spleen, liver, lungs and aorta was investigated. Serum sPLA.sub.2 activity increased from 15213 +- 1131 to a maximum of 32455 +- 4109 nmol/30 on day 21. Maximal increase in sPLA.sub.2 mRNA in paws, lung and aorta was observed on day 14, and in the lymph nodes and spleen on day 28. In the liver, trace levels were found with no corresponding protein expression. In paws, lung, aorta and lymph nodes maximum increase in sPLA.sub.2 protein was noted on day 14 whereas the spleen showed constant sPLA.sub.2 protein level during AA. cPLA.sub.2 mRNA detected in all organs, did not significantly change during the course of AA, with the exception of regional lymph nodes where the message increased between 14 and 28 day. Induction of mRNA and protein of sPLA.sub.2 in several organs is an evidence that AA is a systemic inflammatory process. The parallelity of the sPLA.sub.2 expression to the severity of inflammatory process, implies that sPLA.sub.2 may play pathogenic role in AA. Lack of enhancement of cPLA.sub.2 mRNA may mean that this enzyme is either not induced in AA, or it increases earlier in the course of the inflammatory process. Author Affiliation: (1) Inflammation Research Group and, The Wellesley Central Hospital Research Institute, USA (2) Department of Pathology, The Toronto Hospital, University of Toronto, Ontario, Canada (3) Centre for Biomembranes and Lipid Enzymology, University of Utrecht, The Netherlands (4) Merck Frosst Centre for Therapeutic Research Pointe Claire-Dorval, Quebec, Canada Article History: Registration Date: 03/10/2004