INDUCTION OF NEUTROPHIL MAC-1 INTEGRIN EXPRESSION AND SUPEROXIDE PRODUCTION BY THE MEDICINAL PLANT-EXTRACT GOSSYPOL

Gossypol is present in antiinflammatory poultices made from the medici nal tree Thespesia populnea. Isolated human neutrophils exposed to 3-2 0 mu M gossypol for 15-90 min were assayed in vitro for superoxide pro duction and surface expression of Mac-1 (CD11b/CD18). Gossypol increas ed superoxide production in a time- and concentration-dependent fashio n consistent with a moderate, delayed respiratory burst. Surface Mac-1 expression was increased within 15 min by 3-5 mu M gossypol, resultin g in a 14-fold increase over controls and a threefold greater increase over that produced by PMA. Staurosporine failed to block gossypol ind uction of superoxide and Mac-1, while EDTA inhibited induction of Mac- 1 only, implicating a calcium-dependent mechanism. Gossypol increased intracellular calcium to peak levels, but in a delayed fashion as comp ared to FMLP. These findings demonstrate that gossypol is a highly pot ent stimulant of Mac-1 expression and suggest at least two protein kin ase C-independent pathways of neutrophil activation. The resultant exh austion of neutrophils may account for the antiinflammatory properties of plants containing gossypol.