Prolongation of survival of human polymorphonuclear neutrophils by granulocyte-macrophage colony-stimulating factor is caused by inhibition of programmed cell death

Blood. 1992 Dec 1;80(11):2920-4.

Abstract

In the absence of appropriate stimuli, polymorphonuclear neutrophils (PMN) undergo programmed cell death (PCD), also termed apoptosis. We show that granulocyte-macrophage colony-stimulating factor (GM-CSF), but not the chemotactic factors formyl-methionyl-leucyl-phenylalanine (FMLP), recombinant human (rh) C5a, transforming growth factor (TGF)-beta, and interleukin-8 (IL-8), or other cytokines including IL-3, IL-4, IL-6, and G-CSF, maintains viability of PMN in culture by preventing these cells from undergoing PCD. Prevention from PCD by GM-CSF was associated with induction of RNA and protein synthesis in PMN. Inhibition of RNA and protein synthesis by actinomycin-D and cycloheximide impeded the protection of apoptosis by GM-CSF. Similarly, neutralization of GM-CSF biologic activity by a specific antiserum abrogated GM-CSF-mediated inhibition of PCD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Survival / drug effects*
  • Complement C5a / pharmacology
  • Cycloheximide / pharmacology
  • Cytokines / pharmacology*
  • Dactinomycin / pharmacology
  • Female
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Interleukin-3 / pharmacology
  • Interleukin-4 / pharmacology
  • Interleukin-6 / pharmacology
  • Interleukin-8 / pharmacology
  • Kinetics
  • Male
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / cytology*
  • Neutrophils / drug effects
  • Recombinant Proteins / pharmacology
  • Time Factors
  • Transforming Growth Factor beta / pharmacology

Substances

  • Cytokines
  • Interleukin-3
  • Interleukin-6
  • Interleukin-8
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Granulocyte Colony-Stimulating Factor
  • Dactinomycin
  • Interleukin-4
  • N-Formylmethionine Leucyl-Phenylalanine
  • Complement C5a
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Cycloheximide