CONCEIVABLE DIFFERENCE IN THE ANTIINFLAMMATORY MECHANISMS OF LIPOCORTIN-1 AND LIPOCORTIN-5

HUMAN recombinant lipocortins (LCT) 1 and 5 have been expressed in a y east secretion vector and purified by ion exchange chromatography. The action of the proteins has been investigated in two models of experim ental acute inflammation in the rat: carrageenin induced paw oedema an d zymosan induced pleurisy. The effects of the proteins on PGE2 releas e in vitro by rat macrophages stimulated with zymosan and on rat neutr ophil chemotaxis induced by FMLP have also been assessed. LCT-1 signif icantly inhibited both paw swelling in carrageenin oedema and leukocyt e migration in zymosan pleurisy. Moreover it showed a dose dependent, inhibitory effect on PGE2 release. Neutrophil chemotaxis was only weak ly affected by LCT-1. Conversely LCT-5 did not reduce carrageenin oede ma and slightly inhibited PGE2 release, but showed profound, dose depe ndent inhibitory activity on leukocyte migration in zymosan pleurisy a nd on neutrophil chemotaxis. These data suggest that LCT-1 acts mainly by interfering with arachidonic acid metabolism via the inhibition of phospholipase A2. The anti-inflammatory activity of LCT-5, at varianc e with LCT-1, may be due to a direct effect on cell motility in additi on to the interference with arachidonic acid metabolism.