Bacterial lipopolysaccharides prime human neutrophils for enhanced production of leukotriene B4.
Neutrophils can be "primed" for an enhanced respiratory burst by lipopolysaccharide (LPS) in concentrations measurable in patients with septic shock. Leukotriene B4 (LTB4) is the primary eicosanoid product of neutrophils and is felt to be a mediator of host defense and inflammation. We investigated the in vitro effects of LPS on neutrophil production of LTB4 and the omega-oxidation metabolites of LTB4. Incubation of neutrophils with LPS in concentrations ranging from 0.01 to 100 ng/ml did not result in production of LTB4 or metabolites in the absence of a second stimulus. Priming neutrophils with LPS and then stimulating with opsonized zymosan, phorbol-myristate-acetate or a low concentration of the calcium ionophore A23187 resulted in enhanced production of LTB4. LPS priming of neutrophils occurred in a concentration dependent manner. LPS did not result in LTB4 production in response to the chemoattractant peptide FMLP. LPS priming of neutrophils had no effect on cytosolic calcium concentrations of resting or zymosan-stimulated cells. These results suggest that LPS might effect host defense and tissue injury by potentiating the effect of other stimulants on neutrophil production of LTB4. This LPS induced enhancement may represent an important pathogenetic pathway in patients with gram negative sepsis.
Doerfler
M E
ME
Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892.
Danner
R L
RL
Shelhamer
J H
JH
Parrillo
J E
JE
D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007975:Leukotriene B4 / Q000097:blood*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009895:Opsonin Proteins; D010084:Oxidation-Reduction; D012475:Salmonella; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D008070:Lipopolysaccharides; D009895:Opsonin Proteins; D007975:Leukotriene B4; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium