Premium
Interleukin 1 receptors on rabbit articular chondrocytes: relationship between biological activity and receptor binding kinetics
Author(s) -
Chin Jia En,
Horuk Richard
Publication year - 1990
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.4.5.2137805
Subject(s) - receptor , rabbit (cipher) , kinetics , chemistry , biophysics , receptor–ligand kinetics , microbiology and biotechnology , biology , biochemistry , physics , mathematics , statistics , quantum mechanics
This study gives an account of the biologic and kinetic binding properties of interleukin 1α (IL 1α), interleukin 1β (IL 1β), and Glu‐4 (an NH 2 ‐terminal mutant of IL 1β) 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 E 2 (PGE 2 ) synthesis. IL 1α was 23‐fold more biologically active than IL 1β, which was around 110‐fold more active than Glu‐4 based on the concentration of IL 1 required for half‐maximal stimulation of PGE 2 . The binding of all three ligands was concentration‐dependent and saturable at 4°C. Scatchard analysis of receptor binding data showed that the dissociation constant ( K D ) of IL 1α was 46 ± 12 pM, and the receptor density was 3120 sites/cell. The association of IL 1α at 4°C did not attain equilibrium until after 10 h at 100 pM of 125 I‐labeled IL 1α. The dissociation of bound IL 1α was very slow, t 1/2 of 21 h, although only one class of high‐affinity receptors was detected. The K D of IL 1β binding was 72 ± 3 pM with a receptor density of 800 ± 40 sites/cell. Dissociation of bound 125 I‐labeled IL 1β at 4°C appeared to indicate the presence of two receptor subsets, a fast and a slower component with a t 1/2 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 la and IL 1β are rapidly internalized in chondrocytes in a time‐ and temperature‐dependent manner.— C hin , J. E.; H oruk , R. Interleukin 1 receptors on rabbit articular chondrocytes: relationship between biological activity and receptor binding kinetics. FASEB J. 4: 1481‐1487; 1990.