title: Interleukin 1 receptors on rabbit articular chondrocytes: relationship between biological activity and receptor binding kinetics.
abstract: This study gives an account of the biologic and kinetic binding properties of interleukin 1 alpha (IL 1 alpha), interleukin 1 beta (IL 1 beta), and Glu-4 (an NH2-terminal mutant of IL 1 beta) to interleukin 1 (IL 1) receptors in rabbit articular chondrocytes. All three IL 1's demonstrated full agonist properties in their ability to stimulate prostaglandin E2 (PGE2) synthesis. IL 1 alpha was 23-fold more biologically active than IL 1 beta, which was around 110-fold more active than Glu-4 based on the concentration of IL 1 required for half-maximal stimulation of PGE2. The binding of all three ligands was concentration-dependent and saturable at 4 degrees C. Scatchard analysis of receptor binding data showed that the dissociation constant (KD) of IL 1 alpha was 46 +/- 12 pM, and the receptor density was 3120 sites/cell. The association of IL 1 alpha at 4 degrees C did not attain equilibrium until after 10 h at 100 pM of 125I-labeled IL 1 alpha. The dissociation of bound IL 1 alpha was very slow, t1/2 of 21 h, although only one class of high-affinity receptors was detected. The KD of IL 1 beta binding was 72 +/- 3 pM with a receptor density of 800 +/- 40 sites/cell. Dissociation of bound 125I-labeled IL 1 beta at 4 degrees C appeared to indicate the presence of two receptor subsets, a fast and a slower component with a t1/2 of 2 min and 5 h, respectively. The receptor binding affinity of Glu-4 was 324 +/- 3 pM, in line with its reduced biologic activity. Both IL 1 alpha and IL 1 beta are rapidly internalized in chondrocytes in a time- and temperature-dependent manner.
authors: Medical Products Department, E. I. du Pont de Nemours and Company, Glenolden, Pennsylvania 19036.
authors: J E
authors: JE
authors: Chin
authors: R
authors: R
authors: Horuk
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D007375:Interleukin-1 / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D011817:Rabbits; D011971:Receptors, Immunologic / Q000378:metabolism / Q000502:physiology*; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D015232:Dinoprostone