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 (sPLA2) and cytosolic (cPLA2) phospholipases A2 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 sPLA2 mRNA and protein and mRNA of cPLA2 in paws, regional lymph nodes, spleen, liver, lungs and aorta was investigated. Serum sPLA2 activity increased from 15213 ± 1131 to a maximum of 32455 ± 4109 nmol/30′ on day 21. Maximal increase in sPLA2 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 sPLA2 protein was noted on day 14 whereas the spleen showed constant sPLA2 protein level during AA. cPLA2 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 sPLA2 in several organs is an evidence that AA is a systemic inflammatory process. The parallelity of the sPLA2 expression to the severity of inflammatory process, implies that sPLA2 may play pathogenic role in AA. Lack of enhancement of cPLA2 mRNA may mean that this enzyme is either not induced in AA, or it increases earlier in the course of the inflammatory process.
Similar content being viewed by others
REFERENCES
Klareskog, L. 1989. What can we learn about rheumatoid arthritis from animal models? Springer Semin. Immunopathol. 11:315–33.
Goldings, E. A., and H. E. Jasin. 1989. Arthritis and autoimmunity animals. In: Arthritis and Allied Conditions. Eleventh edition. Edited by D. J. McCarty. Philadelphia, Lea and Febiger. 465–481.
Brahn, E. 1991. Animal models of rheumatoid arthritis. Clues to etiology and treatment. Clin. Orthop. Related Res. 265:42–53.
Greenwald, R. A. 1991. Animal models for evaluation of arthritis drugs. Methods Find Exp. Clin. Pharmacol. 13:75–83.
Whitehorse, M. W. 1975. Adjuvant-induced polyarthritis in rats. In: Handbook of Animal Models for the Rheumatic Diseases. Vol. I. Edited by RA Greenwald, HS Diamond. in Boca Raton, CRC Press, 3–16.
Vadas, P., W. Pruzanski, E. Stefanski, J. Ruse, V. Farewell, J. McLaughlin, and C. Bombardier. 1988. Concordance of endogenous cortisol and phospholipase A2 levels in gram negative septic shock: A prospective study. J. Lab. Clin. Med. 111:584–590.
Vadas, P., B. D. Schouten, E. Stefanski, K. Scott, and W. Pruzanski. 1993. The association of hyperphospholipasemia A2 with multisystem organ failure due to salicylate intoxication. Crit. Care Med. 21:1087–1091.
Koo Seen Lin M., V. Farewell, P. Vadas, A. M. Bookman, E. C. Keystone, and W. Pruzanski. 1996. Secretory phospholipase A2 as an index of activity in rheumatoid arthritis. Prospective double blind study of 212 patients. J. Rheumatol. 23:1162–1166.
Pruzanski, W., K. Albin-Cook, R. Laxer, J. MacMillan, E. Stefanski, P. Vadas, and E. Silverman. 1994. Phospholipase A2 in juvenile rheumatoid arthritis: Correlation to disease type and activity. J. Rheumatol. 21:1951–1954.
Greenwald, R. A., S. A. Moak, N. S. Ramamurthy, and L. M. Golub. 1992. Tetracyclines suppress matrix metalloproteinase activity in adjuvant arthritis and in combination with flurbiprofen, ameliorate bone damage. J. Rheumatol. 19:927–938.
Stefanski, E., W. Pruzanski, B. Sternby, and P. Vadas. 1986. Purification of a soluble phospholipase A2 from synovial fluid in rheumatoid arthritis. J. Biochem. 100:1297–1303.
Van Schaik, R. H. N., N. M. Verhoeven, F. W. Neijs, A. J. Aarsman, and H. van den Bosch. 1993. Cloning of the cDNA coding for 14 kDa group phospholipase A2 from rat liver. Biochem. Biophys. Acta. 1169:1–11.
Goldberg, H. J., M. M. Viegas, B. L. Margolis, J. Schlessinger, and K. Skorecki. 1990. The tyrosine kinase activity of the epidermal-growth-factor receptor is necessary for phospholipase A2 activity. Biochem. J., 267:461–465.
Schalkwjik, C. G., F. Marki, I. Wiesenberg, and H. van den Bosch. 1991. The detection of multimeric forms of phospholipase A2 upon sodium dodecylsulfate-polyacrylamide electrophoresis. J. Lipid Mediat. 4:83–96.
Hadler, N. M. 1996. A pathogenetic model for erosive synovitis. Lessons from animal arthritides. Arthritis Rheum. 19:256–266.
Holoshitz, J., A. Matitiau, and I. R. Cohen. 1984. Arthritis induced by cloned T lymphocytes responsive to Mycobacteria but not to collagen type II. J. Clin. Invest. 73:211–215.
Van Eden, W., J. Holoshitz, Z. Nevo, A. Frenkel, A. Klajman, and I. R. Cohen. 1985. Arthritis induced by a T-lymphocyte clone that responds to Mycobacterium tuberculosis and to cartilage proteoglycans. Proc. Natl. Acad. Sci. U.S.A. 82:5117–5120.
an Eden, W., J. E. R. Thole, R. van der Zee, A. Noordzij, J. D. A. van Embden, E. J. Henson, and I. R. Cohen. 1988. Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature 331:171–173.
Halloran, M. M., Z. Szekanecz, A. E. Koch, S. L. Kunkel, M. D. Burdick, and R. M. Strieter. 1994. Cytokine expression in rat adjuvant-induced arthritis. Arthritis Rheum. 37(M suppl):S215.
Volsen, S. G., P. J. Craig, J. Gauldie, and M. E. J. Billingham. 1990. IL-6 expression at lesion site of adjuvant arthritis. Br. J. Rheumatol. 29(suppl 2):50.
Melli, M. 1988. Assessment of plasma leukotriene and prostaglandin levels during adjuvant arthritis and kaolin-induced paw edema in rats. Prostaglandins Leukot. Essent. Fatty Acids 33:173–178.
Dennis, E. A., 1994. Diversity of group types, regulation, and function of phospholipase A2. J. Biol. Chem. 269:13057–13060.
Balsinde J. and E. A. Dennis. 1996. Distinct roles in signal transduction for each of the phospholipase A2 enzymes present in P388D1 macrophages. J. Biol. Chem. 271:6758–6765.
Crowl, R. M., T. J. Stoller, R. R. Conroy, and C. R. Stoner. 1991. Induction of phospholipase A2 gene expression in human hepatoma cells by mediators of the acute phase response. J. Biol. Chem. 266:2647–2651.
Vadas, P., J. Browning, J. Edelson, and W. Pruzanski. 1993. Extracellular phospholipase A2 expression and inflammation: the relationship with associated disease states. J. Lipid Mediat. 8:1–30.
Nakano, T., O. Ohara, H. Teraoka, and H. Arita. 1990. Glucocorticoids suppress group II phospholipase A2 production by blocking mRNA synthesis and post-transcriptional expression. J. Biol. Chem. 265:12745–12748.
Pfeilschifter, J., W. Pignat, F. Marki, and I. Weisenberg. 1989. Release of phospholipase A2 activity from rat vascular smooth muscle cells is mediated by cAMP. Eur. J. Biochem. 181:237–242.
Bomalaski, J. S., and M. A. Clark. 1993. Phospholipase A2 and arthritis. Arthritis. Rheum. 36:190–198.
Vadas, P., W. Pruzanski, J. Kim and V. Fornasier. 1989. The proinflammatory effect of intra-articular injections of soluble human and venom phospholipase A2. Am. J. Pathol. 134:807–811.
Bomalaski, J. S., P. Lawton, and J. L. Browning. 1991. Human extracellular recombinant phospholipase A2 induces an inflammatory response in rabbit joints. J. Immunol. 146:3904–3910.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lin, M.K.S., Katz, A., Bosch, H.V.D. et al. Induction of Secretory Phospholipase A2 Confirms the Systemic Inflammatory Nature of Adjuvant Arthritis. Inflammation 22, 161–173 (1998). https://doi.org/10.1023/A:1022336006109
Issue Date:
DOI: https://doi.org/10.1023/A:1022336006109