The biosynthesis of endothelin-1 by human polymorphonuclear leukocytes

Biochem Biophys Res Commun. 1991 Jan 31;174(2):613-8. doi: 10.1016/0006-291x(91)91461-k.

Abstract

Human polymorphonuclear leukocytes (PMNs) converted human big endothelin (bET; 2 microM) to an endothelin-1 (ET-1) like contractile factor, as assessed by bioassay. The generation of this ET-1 like activity was rapid (minutes), time-dependent and more pronounced in non-activated cells, suggesting a partial degradation by activated PMNs. Phosphoramidon (54 micrograms/ml) inhibited the formation of this contractile factor, whereas phenylmethylsulfonylfluoride (PMSF; 25 micrograms/ml), pepstatin A (1 microgram/ml) or epoxysuccinyl-L-leucylamido-(guanidino)butane (E-64; 10 micrograms/ml) did not. Incubations of activated PMNs with PMSF significantly potentiated the generation of ET-1 like activity and selectively inhibited the degradation of [125I]ET-1 by activated PMNs. These findings indicate that human PMNs contain and/or release neutral proteases, which can both rapidly produce and degrade ET-1, an observation which may have important (patho)physiologic implications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endothelins / biosynthesis*
  • Endothelins / blood
  • Endothelins / pharmacology
  • Glycopeptides / pharmacology
  • Humans
  • In Vitro Techniques
  • Jugular Veins / drug effects
  • Jugular Veins / physiology
  • Kinetics
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Pepstatins / pharmacology
  • Phenylmethylsulfonyl Fluoride / pharmacology
  • Protease Inhibitors / pharmacology
  • Rabbits

Substances

  • Endothelins
  • Glycopeptides
  • Pepstatins
  • Protease Inhibitors
  • Streptomyces pepsin inhibitor
  • Phenylmethylsulfonyl Fluoride
  • N-Formylmethionine Leucyl-Phenylalanine
  • Leucine
  • E 64
  • phosphoramidon
  • pepstatin