Recombinant interleukin-1 beta interacts with high-affinity receptors to activate neutrophil leukotriene B4 synthesis.
The capacity of interleukin-1 (IL-1) to function as a neutrophil (PMN) activator has been the subject of controversy. While IL-1 purified from mononuclear cell supernatants induced PMN activation, these observations have not been confirmed with recombinant IL-1. To document a cellular basis for a putative PMN-IL-1 interaction, we investigated the presence of IL-1 receptors on the PMN. Using an [35S]methionine-labeled preparation, specific binding of IL-1 to PMNs was demonstrated. Through Scatchard analysis PMNs were calculated to have a mean of 469 +/- 337 receptors per PMN with an affinity (Kd) of 0.32 +/- 0.09 nM. As IL-1 frequently activates arachidonic acid metabolism in other cell types, we investigated eicosanoid production as a putative consequence of the IL-1-PMN interaction. HPLC analysis of extracted supernatants of IL-1-treated PMNs demonstrated the release of leukotriene B4 (LTB4), its oxidative products, and 5-hydroxyeicosatetraenoic acid (5-HETE). Production of LTB4 was quantified using a commercial RIA. LTB4 secretion increased from 17.2 +/- 1.1 to 96.7 +/- 16.4 ng, also with 10.0 ng of IL-1. In time-course studies, it was shown that maximal eicosanoid secretion required a 30-min incubation with IL-1. These observations confirm the proinflammatory activity of IL-1 on neutrophils and resolve the controversy concerning a direct effect of IL-1 on neutrophils. In conclusion, recombinant IL-1 beta interacts with neutrophils through the presence on the PMN of a high-affinity receptor and results in the secretion of arachidonate metabolites.
Borish
L
L
Department of Medicine, New England Medical Center, Tufts Medical School, Boston, Massachusetts 02111.
Rosenbaum
R
R
McDonald
B
B
Rosenwasser
L J
LJ
D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000032:analysis*; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical
D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D007975:Leukotriene B4