Interleukin-1 (IL-1) is a polypeptide cytokine involved in a wide variety of inflammatory and immune reactions. Since the structure of this family of proteins was identified 3 years ago a great deal of new information concerning the biological activity of the recombinant IL-1 protein has accumulated. In spite of this, the actual nature and structure of the receptor binding proteins on the plasma membrane of cells and tissues responsive to IL-1 has not been elucidated. The identification of an IL-1 binding site would be of great interest in trying to identify the precise role of this cytokine in inflammatory and immune reactions. One area in which the role of IL-1 is an important proinflammatory and effector cytokine that has not been well established is in the inflammatory reaction associated with asthma.
The specific aims of this proposal mean to identify and define IL-1 receptors as expressed on allergen specific T cells, polymorphonuclear leukocytes or PMN's and vascular endothelial cells or EC. The biological effects and consequences of IL-1 binding to receptor sites on these tissues will be examined as will an attempt to identify the receptors through the production of specific antisera or monoclonal antibodies. In addition, using a subtraction cloning technique based on the fact that allergen specific T cell clones have been generated that have differential expression of IL-1 receptor sites will be used to generate cDNA libraries enriched for an IL-1 binding protein. Finally, the use of a monoclonal antibody and a cDNA probe for potential IL-1 receptor will be examined on cells and tissues involved in the late phase response of allergic asthma.
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