Ketotifen inhibits PAF-induced actin polymerization in a human eosinophilic leukaemia cell line, EoL-1.
The inhibitory effect of ketotifen on platelet activating factor (PAF)-induced actin polymerization in a human eosinophilic leukaemia cell line, EoL-1, was examined by flow cytometry with the use of reagents specific for the filamentous form of actin (F-actin). Actin polymerization has been considered to be essential for locomotion of cells, chemotaxis and chemokinesis, and thus it reflects the chemotactic reaction of EoL-1 cells stimulated by PAF. Unstimulated EoL-1 cells showed little PAF-induced actin polymerization, whereas EoL-1 cells cultured for 9 days with the supernatant of a human ATL cell line, HIL-3 (HIL-3 sup), showed marked actin polymerization when stimulated with PAF. The actin polymerization in EoL-1 cells induced by PAF was seen in a dose-dependent manner at concentrations of 10(-10) M to 10(-6) M of PAF, and the maximum effect was seen at 10(-7) M of PAF. CV-3988, a specific antagonist of PAF, inhibited 80% of the actin polymerization in EoL-1 cells induced by PAF at a concentration of 10(-5) M. Ketotifen inhibited up to 40% of the PAF-induced actin polymerization of EoL-1 cells in a dose-dependent manner at concentrations of 10(-9) M to 10(-5) M. These results suggest that ketotifen may play an important role in the prevention of eosinophil-induced inflammation in allergic disorders by inhibiting PAF-induced chemotaxis of eosinophils.
Morita
M
M
Dept of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Tsuruta
S
S
Mori
K J
KJ
Mayumi
M
M
Mikawa
H
H
D000199:Actins / Q000378:metabolism*; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D004804:Eosinophils / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007665:Ketotifen / Q000494:pharmacology*; D015472:Leukemia, Eosinophilic, Acute / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011108:Polymers
D000199:Actins; D010972:Platelet Activating Factor; D011108:Polymers; D007665:Ketotifen