Detection and characterization of high affinity plasma membrane receptors for human interleukin 1.

Abstract

Interleukin 1 (IL-1) is a polypeptide hormone that acts as a central mediator of inflammation. Since IL-1 action is presumably mediated by specific cell surface receptor(s), the binding of this hormone to cells was characterized. Purified human IL-1 was labeled to high specific activity with 125I, using Bolton-Hunter reagent. The labeled protein binds specifically to LBRM-33-1A5 (a murine T lymphoma line previously shown to produce IL-2 in response to phytohemagglutinin and IL-1) with an affinity to .apprx. 0.2-2 .times. 1010/M and, at saturation, to .apprx. 500 receptors/cell, on intact cells at 8.degree. C in the presence of sodium azide. The affinity of unmodified IL-1 for the murine plasma membrane receptor is 0.9-2 .times. 1010/M, as measured by the inhibition of 125I-IL-1 binding. The murine receptor specificity was confirmed by demonstrating that, among a series of 12 polypeptide hormones, only IL-1 inhibits 125I-IL-1 binding to LBRM-33-1A5 cells. Treatment of surface-bound 125-I-IL-1 with bivalent water-soluble crosslinkers identified a membrane polypeptide of MW 79,500 to which IL-1 is crosslinked. A variety of cell types were surveyed for the capacity to bind 125I-IL-1 specifically. The presence of specific binding correlates with the capacity of the cells tested to respond to IL-1. The biological effects of the polypeptide hormone IL-1 are mediated by high affinity plasma membrane receptors. The identification of these receptors should provide valuable insight into the apparently diverse biological activities of IL-1.