502 Cell Surface

Interleukin 1 (IL-1), l a polypeptide hormone produced by activated macrophages, has been reported to mediate an apparently diverse range of biological activities (1-3). These include lymphocyte-activating factor (LAF) (4), endogenous or leukocyte pyrogenic activity (5), epidermal cell thymocyte-activating factor (6), bone resorption factor (7, 8), and fibroblast growth factor (9). In general, this set of activities would seem to be consistent with the notion that ILl acts as a soluble mediator during inflammatory responses. We have recently purified to homogeneity a polypeptide secreted by human monocytes that produces several IL-l-like effects (10). The initial step in the action of IL-1 is most likely the binding of this hormone to plasma membrane receptors. The availability of purified IL-1 in our laboratory rendered a search for such receptors possible. For the initial characterization of the plasma membrane (IL-1) receptors, we chose the murine T lymphoma LBRM33-1A5 as a model cell. This cell line produces interleukin 2 in response to suboptimal doses of phytohemagglutinin (PHA) in an IL-l-dependent fashion, and constitutes a well-defined model system for IL-1 action (11, 12). Using radiolabeled human IL-1, we show that these cells bind IL-1 specifically and with high affinity. We further show that cell-bound IL-1 is associated with a membrane protein of -80,000 mol wt. Finally, we have surveyed a broad range of cell types from several species for 125I-IL-1 binding. In general, the data are consistent with the known biological effects of IL-1, in that cell types which bind IL-1 are those previously reported to respond to it. The cell types that showed significant levels of IL-1 binding were either lymphoid in origin or fibroblast/ epithelial type cells. The data support the view that, like other polypeptide hormones, IL-1 action is mediated by a specific plasma membrane receptor protein. The characterization of this protein, both at the functional and structural levels, should aid in understanding the diverse biological activities of IL-1.