Inhibition of human neutrophil NADPH oxidase by Chlamydia serovars E, K, and L2.
The effects of Chlamydia trachomatis (serovars E, K, and L2) on human neutrophil activation were examined with respect to the organisms both as primary agonists and as agents that modulate cell responses to a second stimulus. Unopsonized chlamydiae alone, at ratios of 1.5 to 100 organisms per cell, failed to elicit changes in intracellular calcium or membrane depolarization or to stimulate the respiratory burst or degranulation during 60 min of incubation. Each of these functions except the respiratory burst was also normally activated when chlamydia-infected neutrophils were subsequently stimulated with formylmethionyl leucine phenylalanine or phorbol myristate acetate; the respiratory burst was inhibited 30 to 65%. Inhibition was dependent on live organisms and was maximal within 5 min of incubation. The organisms had no effect on the superoxide (O2-) assay, and the site of chlamydial inhibition was determined at the level of the NADPH oxidase itself, not at an intermediate step in the activation cascade. The mechanism of enzyme inactivation could not be determined. These results show that unopsonized chlamydiae do not elicit responses from infected neutrophils and suggest that microbicidal mechanisms other than those dependent on elaboration of toxic oxygen-derived species are required to inactivate chlamydiae.
Tauber
A I
AI
Department of Medicine, Boston City Hospital, Massachusetts.
Pavlotsky
N
N
Lin
J S
JS
Rice
P A
PA
D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology; D002689:Chlamydia / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000382:microbiology; D005609:Free Radicals; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology; D010101:Oxygen Consumption; D013481:Superoxides / Q000096:biosynthesis
D005609:Free Radicals; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D002118:Calcium