ASPIRIN AND SALICYLATE PREVENT POLYMORPHONUCLEAR LEUKOCYTE SURVIVAL MEDIATED BY PLATELETS AND ACIDOSIS.

MALAVER, ELISA; NEGROTTO, SOLEDAD; PACIENZA, NATALIA; D’ATRI, LINA P; POZNER, ROBERTO G; URDINEZ, PATRICIO; GOMEZ, RICARDO M; SCHATTNER, MIRTA

Roma, Italia

Simposio; XIV International Symposium on Atherosclerosis; 2006

Objectives:Previous works have demonstrated that platelets (PL) delay polymorphonuclear leukocyte (PMN) apoptosis. Considering that acidosis is a feature of the inflammatory areas, we studied platelet-mediated antiapoptotic effect on PMN cultured in acidic medium. We also examined wether NSAIDs (non-steroidal anti-inflammatory drugs) interfere with platelet-mediated prevention of apoptosis. Methods:PMN were obtained from healthy donors and isolated by dextran sedimenation. Platelet-rich plasma was prepared by centrifugation and platelets were washed twice in PBS-prostacyclin-EDTA. PMN and platelets (PMN-PL ratio 1:25) were resuspended in RPMI 1640 supplemented with 2% FBS. Apoptosis was assessed after 18 h by fluorescence microscopy. Results:Extracellular acidosis (pH 6.5) induced a significant inhibition of PMN apoptosis (48 ±6 vs 68 ±4 % apoptosis, p<0.05 n=10). After 36 h culture prevention of PMN apoptosis mediated by either platelets or pH 6.5 was no longer observed (n=3). Pretreatment with aspirin (ASA, 2 mM) and sodium salicylate (NaS, 2mM) at concentrations that per se have no effect on PMN survival, reversed the antiapoptotic effect mediated by acidosis (64 ±5; 64 ±3 n=5) or platelets (59 ±9; 63±9). Indomethacin, a NSAID structurally different from salicylates, had no effect on PMN apoptosis suggesting that ciclooxygenase inhibition is not involved in salicylates action. Conclusions:These results show that while platelets and extracellular acidosis synergize to delay PMN apoptosis, the anti-inflammatory ASA or NaS abrogate these effects.