Stimulus-specific effects of endotoxin on superoxide production by rabbit polymorphonuclear leukocytes.
The release of superoxide (O2-) by polymorphonuclear leukocytes (PMN) is an important function that contributes to microbial death. Controversy exists as to the effect of bacterial endotoxin (lipopolysaccharide, or LPS) on the production of O2-. We have injected rabbits with 25 micrograms Escherichia coli LPS intravenously and studied PMN function 18 to 24 hours later. Relative to PMN from saline-injected controls, PMN from LPS-treated rabbits released markedly greater amounts of O2- in response to 10 ng/ml phorbol myristate acetate (PMA) as measured by nmol cytochrome C reduced in 20 minutes (40.8 +/- 7.8 for LPS-treated PMN versus 10.1 +/- 1.6 for control, p less than 0.01). LPS injection, however, significantly reduced O2- release in response to C (complement) 5a (1.4 +/- 0.6 nmole/20 minutes for LPS-treated PMN versus 5.6 +/- 1.3 nmole/20 minutes for control, p less than 0.01). O2- release in response to a third stimulus, n-formyl-methionyl-leucyl-phenylalanine (10(-7) to 10(-9) M), was not affected by LPS. O2- release in response to PMA was enhanced over a wide range of PMA concentrations (10 to 300 ng/ml). Kinetic studies over 30 minutes indicated that, after a brief initial latency in measurable response, LPS enhanced responsiveness to PMA at all time points observed. The reduced responsiveness to C5a corresponds to a previously reported down regulation of receptors for this ligand after intravenous LPS. The observations indicate that intravenous LPS can alter a critical function of PMN for at least 24 hours in a stimulus-specific manner.
Rosenbaum
J T
JT
Oregon Health Sciences University, Portland 97201.
Enkel
H
H
D000818:Animals; D003182:Complement C5 / Q000008:administration & dosage; D015936:Complement C5a; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D005260:Female; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000008:administration & dosage; D009504:Neutrophils / Q000378:metabolism*; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage
D003182:Complement C5; D008070:Lipopolysaccharides; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D013755:Tetradecanoylphorbol Acetate