LEGIONELLA-PNEUMOPHILA INHIBITS SUPEROXIDE GENERATION IN HUMAN MONOCYTES VIA THE DOWN-MODULATION OF ALPHA-PROTEIN AND BETA-PROTEIN KINASE-CISOTYPES

Legionella pneumophila may subvert monocyte defenses by several mechan isms including the inhibition of phagosome-lysosome fusion or the impa irment of oxidative metabolism. We have investigated the effect if L. pneumophila Knoxville 1, a virulent strain that does not inhibit phago some-lysosome fusion, on the oxidative responsiveness of human monocyt es. Infection of monocytes with L. pneumophila for 48 h resulted in ma rked inhibition of superoxide generation stimulated by phorbol myrista te acetate (PMA) but not by zymosan, a particulate agonist. Evidence i s provided that L. pneumophila interfered with the transductional path way (i.e., protein kinase C, PRC) leading to activation of the NADPH o xidase in monocytes. The phosphorylation of 34-, 48-, 62-, 68-, and 80 -kDa proteins stimulated by PMA was markedly inhibited in infected mon ocytes. In addition, the expression of both alpha and beta PKC isotype s was partially inhibited in infected monocytes. Taken together, our d ata suggest that the down-modulation of PKC isotypes plays a role in t he inhibition of PMA-stimulated superoxide generation.