NOVEL ANTIINFLAMMATORY COMPOUNDS PREVENT CD11B CD18, ALPHA(M)BETA(2) (MAC-1)-DEPENDENT NEUTROPHIL ADHESION WITHOUT BLOCKING ACTIVATION-INDUCED CHANGES IN MAC-1/

Leumedins are small organic molecules with anti-inflammatory propertie s in vivo, We report here that leumedins inhibit the CD11b/CD18 alpha( M) beta(2) (Mac-1)-dependent adherence of neutrophils to serum protein s. The activation of neutrophils leading to adherence via Mac-1 is ass ociated with an increase in cell surface Mac-1 level, and with an incr eased affinity of Mac-1 for adhesion partners. Inhibition of neutrophi l adherence by leumedins does not require blocking the recruitment of Mac-1 from intracellular granules to the cell surface. Furthermore, le umedins do not block the expression on Mac-1 of the epitope for an ''a ctivation-specific'' antibody (CBRM1/5). Time course studies show that leumedins inhibit adherence by targeting an event which occurs concur rently with changes in Mac-I level and induction of the CBRM1/5 epitop e. Therefore, leumedins block an unknown process which is permissive f or Mac-1-dependent adherence.