The inhibitory effect of methotrexate on PAF-induced neutrophil and eosinophil locomotion in asthmatic patients.
We have tested the effect of methotrexate (MTX) on platelet activating factor (PAF)-induced neutrophil and eosinophil locomotion, neutrophil leukotriene B4 (LTB4) generation and mononuclear cell DNA synthesis. Neutrophils from patients treated with low dose methotrexate showed reduced PAF-induced chemotactic responses (727.8 +/- 72.2/10 HPF vs 481.9 +/- 87.3/10 HPF, p < 0.05). Both MTX and the specific PAF antagonist BN-52021 significantly inhibited PAF-induced eosinophil and neutrophil locomotion in a dose-dependent manner. MTX also reduced calcium ionophore-driven LTB4 generation from the neutrophils of asthmatics (358.9 +/- 39.5 pg/10(6) cells vs 240.1 +/- 29.1 pg/10(6) cells, p < 0.05) and attenuated PHA-induced mononuclear DNA synthesis as shown by a reduction in 3H-thymidine uptake and propidium iodide staining. These findings support the view that the beneficial effects of MTX in asthma may be due not only to its anti-mitotic effects on the proliferation of mononuclear cells but also to direct effects on granulocyte locomotion and production of LTB4.
Tsai
J J
JJ
Section of Allergy and Clinical Immunology, Cathay General Hospital, Taipei, Taiwan.
Wang
T F
TF
Wang
S R
SR
D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000276:immunology; D008727:Methotrexate / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*
D010972:Platelet Activating Factor; D007975:Leukotriene B4; D008727:Methotrexate