Peripheral blood neutrophils in chronically neutropenic patients respond to
granulocyte-macrophage colony-stimulating factor with a specific increase
in CR1 expression and CR1 transcription
FD Moore , RM Jack and JH Antin
Department of Medicine, Brigham and Women's Hospital, Harvard Medical
School, Boston, MA 02115.
Chronically neutropenic patients from a phase I/II protocol were studied
for neutrophil (PMN) abnormalities related to therapeutic use of
granulocyte-macrophage colony-stimulating factor (GM-CSF). We analyzed
phenotype by flow cytometry to measure indirect immunofluorescent staining
and activation of transcription by in situ hybridization. PMN count
increased in seven of 17 patients. For the group, PMN expression of
complement receptors, CR1 and CR3, increased after GM-CSF administration (P
less than .005), while expression of class 1 and FcR III was stable. PMN
from both of the patients studied by in situ hybridization demonstrated
increased expression of CR1 transcript, which in one case coincided in time
and intensity with the course of increased CR1 expression, while in the
second case the presence of CR1 mRNA increased but lagged behind the
increased CR1 protein expression. Thus, PMN activation was observed after
GM-CSF infusion, as indicated by increased complement receptor expression.
This effect was due both to translocation of receptors from a preformed
intracellular pool to the cell surface, and to transcriptional regulation
leading to increased receptor synthesis.
Volume 79,
Issue 7,
pp. 1667-1671,
04/01/1992
Copyright © 1992 by The American Society of Hematology