Effect of in vivo desensitization to leukotriene B sub(4) on eosinophil infiltration in response to C5a in guinea-pig skin

• Published in: British journal of pharmacology Vol. 113; no. 1; pp. 117 - 120
• Main Authors: Pettipher, E R, Salter, ED, Showell, HJ
• Format: Journal Article
• Language: English
• Published: 01.01.1994
• ISSN: 0007-1188

The effect of in vivo desensitization to leukotriene B sub(4) (LTB sub(4)) on eosinophil infiltration in response to recombinant C5a was examined in guinea-pig skin. LTB sub(4) and C5a caused a dose-dependent increase in the levels of eosinophil peroxidase activity (a measure of eosinophil infiltration) 4 h after injection into guinea-pig skin. Leukotriene B sub(4) and C5a were approximately equipotent on a molar basis. Platelet activating factor also caused eosinophil accumulation but was much less active than LTB sub(4) or C5a. 20-Hydroxy-LTB sub(4) caused a dose-dependent desensitization of eosinophil responses to LTB sub(4) and partially reduced responses to C5a. At a dose of 20-hydroxy-LTB sub(4) which inhibited responses to LTB sub(4) completely, responses to C5a were reduced by 56.5 plus or minus 1.8%. The structurally related metabolite of 20-hydroxy-LTB sub(4), 20-carboxy-LTB sub(4), which does not cause desensitization to the effects of LTB sub(4), did not inhibit eosinophil infiltration in response to C5a. The LTB sub(4) receptor antagonist, SC-41,930, also inhibited eosinophil accumulation in response to C5a by 63.0 plus or minus 3.9% at a dose which inhibited responses to LTB sub(4) by 86.5 plus or minus 1.9%. These data indicate that eosinophil infiltration in response to C5a may, in part, be mediated by the generation of secondary chemotactic factors such as LTB sub(4).