EFFECTS OF LATRUNCULIN-A ON IMMUNOLOGICAL PHAGOCYTOSIS AND MACROPHAGESPREADING-ASSOCIATED CHANGES IN THE F-ACTIN G-ACTIN CONTENT OF THE CELLS/

Latrunculin A, a toxin from a Red Sea sponge, was shown to be a very p otent inhibitor of immunological phagocytosis by normal and activated macrophages (obtained from mice injected i.p. with LPS), as well as by polymorphonuclear leukocytes. This toxin blocks the interiorization o f the immune complexes but does not interfere with their binding to th e phagocyte (recognition phase); activated macrophages were more susce ptible to this inhibition than normal macrophages and polymorphonuclea r leukocytes. The effect of the toxin on cellular spreading of macroph ages was also studied using two kinds of substrate: glass, and glass c overed with IgG immune complexes. Latrunculin A was able to impair the spreading of normal macrophages on glass covered with immune complexe s, and could also completely reverse the spreading after it had occurr ed, Contrarily, in activated macrophages, this toxin could neither imp ede the spreading nor reverse it, a difference that might be a distinc tive property of the activated state, We have also found that latruncu lin A can reduce the percentage of F-actin in both normal and activate d macrophages, the activated cells being more suceptible to this effec t, Since latrunculin A is a blocking agent of actin polymerization in vitro, these results indicate that actin polymerization and assembly m ust be an essential component of the primary, active event of the engu lfment phase of phagocytosis.