Effects of lipoxin A4 on chemotaxis and degranulation of human eosinophils stimulated by platelet-activating factor and N-formyl-L-methionyl-L-leucyl-L-phenylalanine.
Lipoxins are trihydroxytetraene metabolites derived through a double lipoxygenation of arachidonic acid. Lipoxin A4 (LXA4) was prepared by total chemical synthesis, and its capacity to modulate eosinophil migration has been evaluated. LXA4 is a weak and partial chemotactic agent; at 10(-6) M, it achieved about 20% of the response of 10(-6) M platelet-activating factor (PAF). Preincubation of eosinophils with increasing doses of LXA4 (10(-10)-10(-5) M) resulted in a concentration-dependent inhibition of cell migration induced by 10(-6) M formyl-methionyl-leucyl-phenylalanine (FMLP) and 10(-6) M PAF. The concentration of LXA4 which produced 50% inhibition (IC50) of eosinophil migration was approximately 10(-6) M. LXA4 (10(-10)-10(-6) M) did not elicit ECP release or modulate ECP release induced by 10(-6) M FMLP. LXA4 may have antiallergic properties in preventing eosinophilic migration.
Department of Allergy and Allied Respiratory Disorders, UMDS, Guy's Hospital, London, UK.
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D001798:Blood Proteins / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D044045:Lipoxins; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012260:Ribonucleases
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D010972:Platelet Activating Factor; C040527:lipoxin A4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D012260:Ribonucleases