Legionella pneumophila inhibits superoxide generation in human monocytes via the down-modulation of alpha and beta protein kinase C isotypes.
Legionella pneumophila may subvert monocyte defenses by several mechanisms including the inhibition of phagosome-lysosome fusion or the impairment of oxidative metabolism. We have investigated the effect of L. pneumophila Knoxville 1, a virulent strain that does not inhibit phagosome-lysosome fusion, on the oxidative responsiveness of human monocytes. Infection of monocytes with L. pneumophila for 48 h resulted in marked inhibition of superoxide generation stimulated by phorbol myristate acetate (PMA) but not by zymosan, a particulate agonist. Evidence is provided that L. pneumophila interfered with the transductional pathway (i.e., protein kinase C, PKC) leading to activation of the NADPH oxidase in monocytes. The phosphorylation of 34-, 48-, 62-, 68-, and 80-kDa proteins stimulated by PMA was markedly inhibited in infected monocytes. In addition, the expression of both alpha and beta PKC isotypes was partially inhibited in infected monocytes. Taken together, our data suggest that the down-modulation of PKC isotypes plays a role in the inhibition of PMA-stimulated superoxide generation.
Jacob
T
T
Laboratoire d'Immunologie, Hôpital de Sainte-Marguerite, Marseille, France.
Escallier
J C
JC
Sanguedolce
M V
MV
Chicheportiche
C
C
Bongrand
P
P
Capo
C
C
Mege
J L
JL
D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000502:physiology*; D016952:Legionella pneumophila / Q000502:physiology*; D009000:Monocytes / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000032:analysis / Q000378:metabolism; D019255:NADPH Oxidases; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000737:chemistry / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D007527:Isoenzymes; D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate