Recombinant interleukin-1 beta interacts with high-affinity receptors to activate neutrophil leukotriene B4 synthesis

Inflammation. 1990 Apr;14(2):151-62. doi: 10.1007/BF00917454.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Humans
  • In Vitro Techniques
  • Interleukin-1 / pharmacology*
  • Leukotriene B4 / biosynthesis*
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Receptors, Immunologic / analysis*
  • Receptors, Interleukin-1
  • Recombinant Proteins / pharmacology
  • Stimulation, Chemical

Substances

  • Interleukin-1
  • Receptors, Immunologic
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Leukotriene B4