Granulocyte colony-stimulating factor induces hFc gamma RI (CD64 antigen)-positive neutrophils via an effect on myeloid precursor cells.
In this study we have examined hFc gamma RI expression during myelopoiesis. Normal bone marrow (BM) cells were found to express hFc gamma RI up to the metamyelocyte stage. A different Fc gamma RI expression pattern was observed in an in vitro model of myelopoiesis. Purified CD34-positive BM cells, cultured for 12 to 14 days with granulocyte colony-stimulating factor (G-CSF), differentiate into a population of mature granulocytic cells. In these cultures, in which hFc gamma RI was virtually absent on the initial CD34-positive BM cells, hFc gamma RI was strongly induced by G-CSF after only 5 days. During final maturation the cells remained hFc gamma RI positive. This expression was confirmed functionally by antibody-sensitized erythrocytes (EA)-rosette assays. Moreover, the mature myeloid cells were found to express mRNA encoding for hFc gamma RI, whereas reverse-transcriptase polymerase chain reaction analysis showed that both hFc gamma RIA and hFc gamma RIB genes were expressed. In contrast, on peripheral blood (PB) polymorphonuclear neutrophil leukocytes (PMN) the in vitro effect of G-CSF as to hFc gamma RI induction was limited. Therefore, we conclude that, with respect to hFc gamma RI expression on PMN, G-CSF acts on myeloid precursor cells rather than on mature cells. This conclusion could be strengthened by in vivo administration of a single dose of G-CSF to a healthy volunteer. After a 12-hour lag time, hFc gamma RI expressing PMNs were detected in the peripheral blood. This study shows that hFc gamma RI is an early myeloid differentiation marker that is lost during normal final maturation. However, committed myeloid progenitor cells can be strongly induced by G-CSF to express hFc gamma RI, ultimately resulting in mature granulocytic cells expressing the high-affinity receptor for IgG. This expression may have important consequences for the functional capacity of these cells.
Kerst
J M
JM
Central Laboratory of the Red Cross Blood Transfusion Service, Amsterdam, The Netherlands.
van de Winkel
J G
JG
Evans
A H
AH
de Haas
M
M
Slaper-Cortenbach
I C
IC
de Wit
T P
TP
von dem Borne
A E
AE
van der Schoot
C E
CE
van Oers
R H
RH
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D001483:Base Sequence; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D017452:Receptors, IgG / Q000032:analysis*
D015703:Antigens, CD; D018952:Antigens, CD34; D017452:Receptors, IgG; D016179:Granulocyte Colony-Stimulating Factor