Induction of Fc gamma R-III (CD16) expression on neutrophils affected by paroxysmal nocturnal haemoglobinuria by administration of granulocyte colony-stimulating factor

Br J Haematol. 1993 Jul;84(3):497-503. doi: 10.1111/j.1365-2141.1993.tb03107.x.

Abstract

The inducibility of glycosyl-phosphatidylinositol (GPI)-anchored proteins on affected paroxysmal nocturnal haemoglobinuria (PNH) neutrophils (PMN) after both in vitro and in vivo stimulation was investigated. Fc gamma R-III (CD16), decay-accelerating factor (DAF/CD55) and 20 kD homologous restriction factor (HRF20/CD59) were demonstrated to be concurrently deficient on unstimulated defective PNH PMN. Upon in vitro stimulation with either N-formyl-methionyl-leucyl-phenylalanine (fMLP), zymosan-activated serum (ZAS), or recombinant human granulocyte colony-stimulation factor (G-CSF), neither CD16 nor CD55 expression was induced on defective PNH PMN. G-CSF was administered to two patients with PNH when their conditions were complicated by bacterial infections, or to prevent infections associated with the extraction of teeth or cataract surgery. CD16 expression was induced on the defective PNH PMN in both cases during the administration of G-CSF, but the expression of CD55 and CD59 was not. CD16, induced on the defective PNH PMN during the administration of G-CSF, was phosphatidylinositol-specific phospholipase C (PIPLC)-sensitive, implying that it had GPI-linkage to the membranes. The patients treated with G-CSF recovered from infection or evaded infection. These observations suggest that a deficiency of GPI-anchored proteins is not always seen in defective PNH blood cells, at least under certain stimulation conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis
  • CD55 Antigens
  • CD59 Antigens
  • Cells, Cultured
  • Complement Inactivator Proteins / analysis
  • Granulocyte Colony-Stimulating Factor / immunology*
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hemoglobinuria, Paroxysmal / drug therapy
  • Hemoglobinuria, Paroxysmal / immunology*
  • Humans
  • Male
  • Membrane Glycoproteins / analysis
  • Middle Aged
  • Neutrophils / immunology*
  • Phosphatidylinositol Diacylglycerol-Lyase
  • Phosphoinositide Phospholipase C
  • Phosphoric Diester Hydrolases / pharmacology
  • Receptors, IgG / analysis*
  • Receptors, IgG / drug effects

Substances

  • Antigens, CD
  • CD55 Antigens
  • CD59 Antigens
  • Complement Inactivator Proteins
  • Membrane Glycoproteins
  • Receptors, IgG
  • Granulocyte Colony-Stimulating Factor
  • Phosphoric Diester Hydrolases
  • Phosphoinositide Phospholipase C
  • Phosphatidylinositol Diacylglycerol-Lyase