Inhibitory effect of gabexate mesilate on human neutrophil function.
Neutrophils accumulated in the lung are thought to play a key role in the pathogenesis of adult respiratory distress syndrome and interstitial pneumonia following bone-marrow transplantation. The effects of gabexate mesilate on several aspects of human neutrophil function have been investigated. Gabexate mesilate significantly decreased both the generation of reactive oxygen species (O2-, H2O2, OH.) by neutrophils and neutrophil chemotaxis. In contrast, the drug did not affect the levels of reactive oxygen species generated by a cell-free reactive-oxygen-species generating system. Intracellular calcium concentrations in neutrophils stimulated by f-Met-Leu-Phe were decreased in the presence of gabexate mesilate. These data suggest that the reduction in reactive-oxygen-species production and neutrophil chemotaxis by gabexate mesilate may contribute to the effectiveness of the drug in adult respiratory distress syndrome and interstitial pneumonia after bone-marrow transplantation. The suppression of the increase in intracellular calcium concentration may at least be responsible for the inhibition of these neutrophil functions by gabexate mesilate.
Mikawa
K
K
Department of Anaesthesiology, Kobe University School of Medicine, Japan.
Akamatsu
H
H
Maekawa
N
N
Nishina
K
K
Obara
H
H
Niwa
Y
Y
D002118:Calcium / Q000097:blood; D002470:Cell Survival; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016670:Gabexate / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D066298:In Vitro Techniques; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000032:analysis; D012016:Reference Values; D019820:Xanthine; D014969:Xanthine Oxidase; D014970:Xanthines
D017382:Reactive Oxygen Species; D014970:Xanthines; D019820:Xanthine; D016670:Gabexate; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D002118:Calcium