The antifolate 10-deazaaminopterin inhibits neutrophil chemotaxis and superoxide generation.
The effect of the dihydrofolate reductase inhibitor 10-deazaaminopterin on several neutrophil functions was tested in vitro. At 100 uM it inhibited chemotaxis by 50% and reduced the generation of superoxide by 30%. It had no influence on phagocytosis and did not significantly change the secretion of beta-D-glucuronidase, a marker enzyme of degranulation. After preincubation of white cells with various concentrations of 10-deazaaminopterin, followed by resuspension in drug-free medium, no inhibition of chemotaxis or superoxide generation was seen. Therefore, the effects on chemotaxis and NADPH oxidase appear to be reversible and not due to metabolic transformation of the dihydrofolate reductase inhibitor.
Weber
G F
GF
College of Medicine, Department of Biochemistry, University of South Alabama, Mobile 36688.
Nair
M G
MG
McCord
J M
JM
D000328:Adult; D000630:Aminopterin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*
D005493:Folic Acid Antagonists; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005492:Folic Acid; D000630:Aminopterin; C017178:10-deazaaminopterin; D008727:Methotrexate