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 interstiti al pneumonia following bone-marrow transplantation. The effects of gab exate mesilate on several aspects of human neutrophil function have be en investigated. Gabexate mesilate significantly decreased both the ge neration of reactive oxygen species (O-2(-), H2O2, OH.) by neutrophils and neutrophil chemotaxis. In contrast, the drug did not affect the l evels of reactive oxygen species generated by a cell-free reactive-oxy gen-species generating system. Intracellular calcium concentrations in neutrophils stimulated by f-Met-Leu-Phe were decreased in the presenc e of gabexate mesilate. These data suggest that the reduction in react ive-oxygen-species production and neutrophil chemotaxis by gabexate me silate may contribute to the effectiveness of the drug in adult respir atory distress syndrome and interstitial pneumonia after bone-marrow t ransplantation. The suppression of the increase in intracellular calci um concentration may at least be responsible for the inhibition of the se neutrophil functions by gabexate mesilate.