Peripheral blood neutrophils in chronically neutropenic patients respond to granulocyte-macrophage colony-stimulating factor with a specific increase in CR1 expression and CR1 transcription.
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.
Moore
F D
FD
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Jack
R M
RM
Antin
J H
JH
D000954:Antigens, Surface / Q000235:genetics; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count; D009503:Neutropenia / Q000097:blood* / Q000188:drug therapy; D009504:Neutrophils / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011951:Receptors, Complement / Q000235:genetics*; D017463:Receptors, Complement 3b; D011994:Recombinant Proteins / Q000627:therapeutic use; D014158:Transcription, Genetic
D000954:Antigens, Surface; D012333:RNA, Messenger; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor