Regulation of human neutrophil degranulation by LY-83583 and L-arginine: Role of cGMP-dependent protein kinase

T. A. Wyatt, T. M. Lincoln, K. B. Pryzwansky

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

The effects of guanosine 3,'5'-cyclic monophosphate (cGMP) on the secretory response of activated human neutrophils were investigated using LY- 83583, an inhibitor of soluble guanylate cyclase, and L-arginine, the precursor of nitric oxide formation. A 30% release of myeloperoxidase (MPO) and lactoferrin (LF) from the primary and specific granules, respectively, was detected by enzyme-linked immunosorbent assay in adhered neutrophils stimulated with 0.1 μM N-formyl-methionyl-leucyl-phenylalanine (FMLP) or 20 μM A-23187. LY-83583 (100 μM) inhibited the release of both LF and MPO after stimulation with FMLP or A-23187. Conversely, preincubation of neutrophils with 0.5 mM L-arginine augmented the release of LF and MPO in FMLP- and A-23187-stimulated cells. Concurrent with the increase in the degranulation response was an elevation of cGMP levels in L-arginine-treated cells, while stimulated cGMP levels were reduced in LY-83583-treated cells. Furthermore, cGMP-dependent protein kinase (G-kinase) activity was reduced in LY-83583-treated cells, as determined by the delay in G-kinase translocation to intermediate filaments and the inhibition of vimentin phosphorylation. Degranulation, elevation of cGMP levels, and targeting of G-kinase were also dependent on the concentration of A-23187 or FMLP. These data suggest that activators of neutrophil degranulation mediate this response through a cGMP- dependent protein kinase mechanism.

Original languageEnglish (US)
Pages (from-to)C201-C211
JournalAmerican Journal of Physiology - Cell Physiology
Volume265
Issue number1 34-1
StatePublished - Jan 1 1993

    Fingerprint

Keywords

  • A-23187
  • N-formyl-methionyl- leucyl-phenylalanine
  • guanosine 3',5'-cyclic monophosphate
  • phosphorylation
  • secretion
  • vimentin

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this