Species-specific binding of IL-1, but not the IL-1 receptor antagonist, by fibroblasts.
Our laboratory previously reported that bovine thymocytes and fibroblasts proliferated only in response to bovine IL-1, whereas proliferation of murine thymocytes was augmented equally well by murine, human, and bovine IL-1. In this study, we used direct and competitive receptor binding assays to determine whether differential binding of homologous versus heterologous IL-1 accounts for the species-specific response of bovine fibroblasts. Our results demonstrated that bovine and human fibroblasts bound homologous IL-1 with high affinity and heterologous IL-1 with lower affinity. In contrast, murine fibroblasts bound both homologous and heterologous IL-1 with high affinity. Because IL-1 and the human IL-1 receptor antagonist (IL-1ra) both bind to type 1 IL-1 receptors, we also determined whether the IL-1ra demonstrated receptor binding properties similar to human IL-1 for bovine, human, and murine fibroblasts. To our surprise, the human IL-1ra bound equally well to bovine, human and murine fibroblasts. We used this characteristic of the IL-ra to perform affinity cross-linking analysis of the IL-1 receptors on bovine, human and murine fibroblasts. These comparisons demonstrated the IL-1 receptors on bovine and human fibroblasts have similar molecular sizes (M(r) 73 kDa and M(r) kDa, respectively), whereas, IL-1 receptors on murine fibroblasts have an estimated molecular size of M(r) 88 kDa. These data demonstrate that IL-1 receptors on bovine fibroblasts preferentially bind homologous IL-1, but bovine fibroblasts do not discriminate binding by the human IL-1ra. In contrast, murine fibroblast IL-1 receptors bind heterologous IL-1 with high affinity.
Department of Pathobiological Sciences, University of Wisconsin, School of Veterinary Medicine, Madison 53706.
J A
JA
Lederer
C J
CJ
Czuprynski
D016475:3T3 Cells; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007700:Kinetics; D051379:Mice; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism*; D012867:Skin / Q000276:immunology / Q000378:metabolism*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007457:Iodine Radioisotopes; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins