INDUCTION OF FC-GAMMA-R-III (CD16) EXPRESSION ON NEUTROPHILS AFFECTEDBY PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA BY ADMINISTRATION OF GRANULOCYTE-COLONY-STIMULATING FACTOR

The inducibility of glycosyl-phosphatidylinositol (GPI)-anchored prote ins on affected paroxysmal nocturnal haemoglobinuria (PNH) neutrophils (PMN) after both in vitro and in vivo stimulation was investigated. F cgammaR-III (CD16), decay-accelerating factor (DAF/CD55)and 20 kD homo logous restriction factor (HRF20/CD59) were demonstrated to be concurr ently deficient on unstimulated defective PNH PMN. Upon in vitro stimu lation with either N-formyl-methionyl-leucyl-phenylalanine (fMLP), zym osan-activated serum (ZAS), or recombinant human granulocyte colony-st imulation 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 catarac t surgery. CD16 expression was induced on the defective PNH PMN in bot h 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 a dministration of G-CSF, was phosphatidylinositol-specific phospholipas e C (PIPLC)-sensitive, implying that it had GPI-linkage to the membran es. The patients treated with G-CSF recovered from infection or evaded infection. These observations suggest that a deficiency of GPI-anchor ed proteins is not always seen in defective PNH blood cells, at least under certain stimulation conditions.