Modulation of eosinophil recruitment in the rat by the platelet-activating factor (PAF) antagonist, BN 52021, the somatostatin analog, BIM 23014, and by cyclosporin A.
The factors responsible for in vivo eosinophil recruitment are poorly defined, although T-lymphocytes appear to be involved in the etiology of eosinophilia. In order to clarify this relationship, we studied the modulation of eosinophil mobilization in the rat after immune challenge, by chronic treatment with the PAF-antagonist, BN 52021, the somatostatin analog, BIM 23014 and with Cyclosporin A (CsA). In rats made hypereosinophilic by pretreatment with cyclophosphamide or sephadex, a significant increase of the eosinophil count in blood and peritoneal fluid was induced by anaphylactic reaction. CsA totally abolished both hypereosinophilia and peritoneal eosinophil infiltration. BIM 23014 also, significantly reduced the circulating eosinophils (-68%, p less than 0.001) and cell infiltration (-86%, p less than 0.05). In contrast, BN 52021 decreased peritoneal eosinophil recruitment, while having relatively little effect on circulating cells. CsA and somatostatin are known to affect T-cell proliferation, and as T-cells are involved in the differentiation of hematopoietic cells into eosinophils, these drugs could decrease eosinophil availability for recruitment. In contrast, the PAF antagonist may act by inhibiting PAF-induced eosinophil chemotaxis, providing a more specific inhibition of this process than that exerted by CsA, BIM 23014 and other immunosuppressive agents.
Etienne
A
A
I.H.B. Research Laboratories, ZA de Courtaboeuf, Les Ulis, France.
Soulard
C
C
Thonier
F
F
Braquet
P
P
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D004224:Diterpenes; D004804:Eosinophils / Q000187:drug effects*; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000031:analogs & derivatives*
D003524:Cyclosporins; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010456:Peptides, Cyclic; D010972:Platelet Activating Factor; C060347:lanreotide; D013004:Somatostatin; D003520:Cyclophosphamide; C045856:ginkgolide B