POLYMORPHONUCLEAR LEUKOCYTE APOPTOSIS, A NEW TARGET FOR ASPIRIN AND SODIUM SALICYLATE ANIINFLAMMATORY ACTION

NEGROTTO S; MALAVER E; ALVAREZ ME; PACIENZA N; D'ATRI LP; POZNER RG; LAZZARI MA; GÓMEZ RM; SCHATTNER M

Córdoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología (ALAI); 2005

Aspirin (ASA) and sodium salicylate (NaSal) are widely prescribed agents used to treat inflammation. During inflammation, several factors prolong polymorphonuclear leukocytes (PMN) survival. We examined whether salicylates interfere with PMN apoptosis. Preincubation of PMN with ASA or NaSal suppressed the prolonged PMN survival mediated by LPS (0.5ug/ml) (EC50: 1.35mM and 1.53mM respectively). The effect of salicylates was not specific to LPS since the apoptosis delay mediated by G-CSF or pH 6.5 was also markedly inhibited (71, 45 and 57% apoptosis for control, G-CSF and pH 6.5 without ASA and 70, 58 and 67% with 1mM ASA, n=5). Although ASA or NaSal alone did not trigger apoptosis (1-10mM) (n=5), both drugs significantly increased PMN apoptosis mediated by Zymozan (15 without ASA and 19, 22, 28 % of apoptosis with 1, 2 and 3mM ASA or NaSal, n=4). Indomethacin (1-50uM), a nonsalicylate inhibitor of COX, did not inhibit the LPS or GSF antiapoptotitc activity (n=4). The prolonged PMN survival mediated by cytokines was no longer observed in PMN obtained from donors who had ingested ASA (2g) (n=7). These findings reveal that another mechanism by which salicylates exert its antiinflammatory action is by shortening the PMN life span.