Detection and characterization of high affinity plasma membrane receptors for human interleukin 1.
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), we have characterized the binding of this hormone to cells. 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 of approximately 0.2-2 X 10(10)/M and, at saturation, to approximately 500 receptors per cell, on intact cells at 8 degrees C in the presence of sodium azide. The affinity of unmodified IL-1 for the murine plasma membrane receptor is 0.9-2 X 10(10)/M, as measured by the inhibition of 125I-IL-1 binding. The murine receptor specificity has been 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 125I-IL-1 with bivalent water-soluble crosslinkers identified a membrane polypeptide of Mr 79,500 to which IL-1 is crosslinked. A variety of cell types have been 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. Our results indicate that 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.
Dower
S K
SK
Kronheim
S R
SR
March
C J
CJ
Conlon
P J
PJ
Hopp
T P
TP
Gillis
S
S
Urdal
D L
DL
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D003432:Cross-Linking Reagents; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology* / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D008223:Lymphoma / Q000276:immunology; D051379:Mice; D011971:Receptors, Immunologic / Q000302:isolation & purification* / Q000502:physiology; D017472:Receptors, Interleukin-1
D003432:Cross-Linking Reagents; D007375:Interleukin-1; D007376:Interleukin-2; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1