Stimulus-specific effects of endotoxin on superoxide production by rabbit polymorphonuclear leukocytes

• Published in: The Yale journal of biology & medicine Vol. 60; no. 5; pp. 391 - 396
• Main Authors: Rosenbaum, J T, Enkel, H
• Format: Journal Article
• Language: English
• Published: United States Yale Journal of Biology and Medicine 01.09.1987
• Subjects: Animals; Complement C5 - administration & dosage; Complement C5a; Dose-Response Relationship, Drug; Escherichia coli; Female; Injections, Intravenous; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - pharmacology; N-Formylmethionine Leucyl-Phenylalanine - administration & dosage; Neutrophils - metabolism; Rabbits; Superoxides - metabolism; Tetradecanoylphorbol Acetate - administration & dosage
• ISSN: 0044-0086; 1551-4056

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.