Presence of IL-1 receptors on human and murine neutrophils. Relevance to IL-1-mediated effects in inflammation.
Inflammatory responses are characterized by the infiltration of polymorphonuclear neutrophils (PMN) at the involved site. IL-1 may have an important role in mediating this response, but whether IL-1 acts directly on PMN is controversial. In this study, we examined PMN for the presence of IL-1R and determined the effect of IL-1 on PMN migration in vivo. Thioglycollate, proteose-peptone, or IL-1 elicited peritoneal exudate cells were found to bind 125I-IL-1 alpha in a specific and saturable manner. This binding was localized to the PMN in the exudate. Scatchard plot analysis indicates the presence of approximately 1700 receptors per PMN and an apparent dissociation constant of 3.0 x 10(-10) M. Binding sites for 125I-IL-1 alpha were also found on human PMN prepared from peripheral blood. There are approximately 900 receptors per cell on human PMN with a dissociation constant similar to that observed for elicited murine PMN. Binding of 125I-IL-1 alpha to the mouse and human PMN is inhibited by both recombinant human IL-1 alpha and IL-1 beta, indicating that both IL-1 proteins bind to the same receptor on these cells. Human PMN were able to internalize radioiodinated IL-1. We conclude that PMN possess receptors for IL-1 and that these binding sites may be important in mediating IL-1 effects on granulocytes that are involved in the inflammatory response.
Parker
K P
KP
Department of Immunopharmacology, Hoffmann-LaRoche, Inc., Nutley, NJ 07110.
Benjamin
W R
WR
Kaffka
K L
KL
Kilian
P L
PL
D000818:Animals; D001202:Ascitic Fluid; D001667:Binding, Competitive; D002364:Caseins / Q000008:administration & dosage; D002465:Cell Movement / Q000187:drug effects; D002469:Cell Separation; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007375:Interleukin-1 / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage; D011971:Receptors, Immunologic / Q000032:analysis*; D017472:Receptors, Interleukin-1; D013864:Thioglycolates
D002364:Caseins; D007375:Interleukin-1; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D013864:Thioglycolates; C018135:proteose-peptone