Lexipafant Inhibits Platelet Activating Factor Enhanced Neutrophil Functions
| Autor: | Chad E. Jacobs, Aubrey C. Galloway, Jess D. Schwartz, Daniel S. Schwartz, Federico Steiner, Stephen B. Colvin, Majid Tayyarah, Stuart G. Marcus, Eugene A. Grossi, Kenneth Eng, Peter Shamamian |
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| Rok vydání: | 1997 |
| Předmět: |
medicine.medical_specialty
Free Radicals Neutrophils medicine.drug_class Macrophage-1 Antigen Granulocyte Biology Flow cytometry chemistry.chemical_compound Leucine Superoxides Internal medicine medicine Humans Platelet Activating Factor Respiratory Burst Dose-Response Relationship Drug medicine.diagnostic_test Platelet-activating factor Superoxide Elastase Imidazoles Temperature Antagonist Receptor antagonist Molecular biology Endocrinology medicine.anatomical_structure chemistry Cell culture Surgery Leukocyte Elastase |
| Zdroj: | Journal of Surgical Research. 69:240-248 |
| ISSN: | 0022-4804 |
| Popis: | Platelet activating factor (PAF) enhances polymorphonuclear leukocyte (PMN) superoxide (.O2-) production, CD11b expression, and elastase release, all essential components in the pathophysiology of multiple-organ failure. This study was designed to determine the effects of Lexipafant, a PAF receptor antagonist, on PAF-mediated PMN functions. PMNs from 10 healthy volunteers were isolated and pretreated with various concentrations of Lexipafant (0-100 microM). PMNs were then incubated for 5 min with 200 nM PAF for .O2- detection or 2000 nM PAF for elastase measurement and activated with 1 microM N-formylmethionylleucylphenylalanine. The mean rate of .O2- production was determined by a cytochrome c reduction assay (nmole .O2-/min/1.33 x 10(5) PMN +/- SEM). Elastase release was measured by the cleavage of the synthetic elastase substrate Meo-Suc-Ala-Ala-Pro-Val-pNA (mean elastolytic activity +/- SEM). In parallel experiments, PMNs were incubated with 200 nM PAF for 30 min following pre-treatment with Lexipafant and CD11b expression was determined by flow cytometry (mean fluorescence intensity +/- SEM). Statistical analysis was performed using repeated-measures ANOVA (P0.05). Lexipafant inhibited PAF-enhanced PMN .O2- generation, CD11b expression and elastase release in a dose dependent fashion. The IC50 of Lexipafant for .O2- production, CD11b expression, and elastase release was 0.046, 0.285, and 0.05 microM, respectively. Lexipafant attenuated the PAF-mediated upregulation of PMN .O2- production, CD11b expression, and elastase release in a dose dependent fashion. These data support the hypothesis that Lexipafant may reduce the severity of the inflammatory response to injury produced by PAF-enhanced activation of PMNs. |
| Databáze: | OpenAIRE |
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