The effect of pentamidine salts on the respiratory burst of human neutrophilic granulocytes.
Therapeutic concentrations (0.3-1.5 mg/l) of pentamidine isethionate and pentamidine mesylate, obtained after parenteral administration of either drug, did not affect oxygen consumption in the stimulated neutrophilic granulocyte. At concentrations of 0.7, 1.1 and 1.5 mg/l, superoxide production, hydrogen peroxide production, myeloperoxidase (MPO)-mediated iodination and hexose monophosphate shunt activity were suppressed relative to untreated cells (P less than 0.001 in each case). The depression in each activity was dose-related. There was no significant difference between the drugs with regard to these impairments in neutrophilic granulocyte function. This lowered respiratory burst activity, which would lead to a depression of MPO-dependent and MPO-independent processes in stimulated neutrophilic granulocytes, may be due to drug induced dysfunction of NADPH-oxidase.
Arnott
M A
MA
Department of Microbiology, The University, Leicester, UK.
Hay
J
J
D006098:Granulocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D010419:Pentamidine / Q000494:pharmacology*; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D010419:Pentamidine; D006861:Hydrogen Peroxide; D009195:Peroxidase