Mobilization and extracellular release of granular enzymes from human leukocytes during phagocytosis: inhibition by colchicine and cortisol but not by salicylate

Granular (lysosomal) enzymes are released from phagocytizing human leukocytes and are believed to be important in the tissue damage of acute inflammation. Antiinflammatory drugs such as colchicine, cortisol, and salicylate have been reported to “stabilize” isolated lysosomes or to inhibit degranulation within cells. These drugs, by altering mobilization of granular enzymes within cells, might be expected to affect the release of these enzymes outside of cells. Human blood leukocytes, isolated by dextran sedimentation, were incubated in autologous serum‐buffer media, with or without colchicine (2.5 × 10 −5 M), cortisol (5 × 10 −4 M), Na salicylate (2.2 × 10 −3 M), or acetylsalicylic acid (10 −3 M), for 30 minutes, 37.5° C, and then with or without heat‐killed staphylococci. Both cellular and extracellular activities of granular enzymes (lysozyme, acid phosphatase, cathepsin) were measured. Both intracellular mobilization and extracellular release of granular enzymes by phagocytizing leukocytes are inhibited by colchicine and cortisol. Salicylate, contrary to suggestions based on studies with isolated lysosomes from liver, did not show these effects. These results may account in part for antiinflammatory effects of colchicine and cortisol, but not of salicylate.