Restoration of phagocyte function by interferon-gamma in X-linked chronic
granulomatous disease occurs at the level of a progenitor cell
RA Ezekowitz, CA Sieff, MC Dinauer, DG Nathan, SH Orkin and PE Newburger
Division of Hematology/Oncology, Children's Hospital, Boston, MA 02115.
Phagocytes from X-linked chronic granulomatous disease (X-CGD) patients are
deficient in their ability to generate superoxide because of a defective
gene that encodes a heavy chain of cytochrome b, a critical component in
the superoxide-generating pathway. Previously we have shown that a single
in vivo treatment of selected X-CGD patients with interferon-gamma
(INF-gamma) resulted 14 days later in near-normal levels of superoxide
generation by phagocytes. The effect persisted for 28 days. This prolonged
effect suggested that the lymphokine affected progenitor cells. In this
study, we examined progenitor-derived colonies from the peripheral blood
from this unusual X-CGD kindred. Progenitor-derived colonies examined
before treatment were unable to generate superoxide as visualized by lack
of nitro blue tetrazolium (NBT) reduction compared with normal controls. By
contrast, colonies derived 7 days after a single INF-gamma injection were
able to generate superoxide as shown by increased NBT reduction. Colonies
harvested 21 days after treatment contained only rare cells capable of NBT
reduction. Our results indicate that INF-gamma can reprogram the myeloid
progenitor cells to express a partially corrected phenotype. This corrected
phenotype is later expressed in daughter cells.
Volume 76,
Issue 12,
pp. 2443-2448,
12/15/1990
Copyright © 1990 by The American Society of Hematology
