Recombinant granulocyte colony-stimulating factor administration to healthy volunteers: induction of immunophenotypically and functionally altered neutrophils via an effect on myeloid progenitor cells.
We performed a detailed kinetic study on the in vivo effect of a single subcutaneous dose of granulocyte colony-stimulating factor (G-CSF; 300 micrograms) in four healthy individuals on the expression and function of neutrophil Fc gamma receptors (Fc gamma R). G-CSF did not induce Fc gamma RI (CD64) on circulating neutrophils. However, neutrophils newly formed in response to G-CSF were Fc gamma RI positive and were able to perform antibody-dependent cellular cytotoxicity in an Fc gamma RI-dependent way. Fc gamma RII (CD32) expression was not changed significantly. Fc gamma RIII (CD16, phosphatidylinositol-linked) expression, slightly increased immediately (30 minutes) postinjection, was found to be strongly decreased on the newly formed population. For comparison, we studied the expression of the PI-linked proteins leukocyte alkaline phosphatase (LAP) and CD14. Intracellular levels of LAP mirrored the biphasic expression pattern as membrane-bound Fc gamma RIII. In contrast, CD14 expression on neutrophils was initially constant, followed by high levels on the newly formed neutrophils. Soluble CD14 levels were found to be elevated transiently, whereas peak levels of soluble Fc gamma III were observed as late as 6 days postinjection. In conclusion, we have shown that G-CSF results in an immunophenotypically and functionally altered neutrophil population for an important part as a result of its effect on myeloid precursor cells.
Kerst
J M
JM
Central Laboratory of the Red Cross Blood Transfusion Service, Amsterdam, The Netherlands.
de Haas
M
M
van der Schoot
C E
CE
Slaper-Cortenbach
I C
IC
Kleijer
M
M
von dem Borne
A E
AE
van Oers
R H
RH
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015152:Blotting, Northern; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D016130:Immunophenotyping; D007958:Leukocyte Count; D018950:Lipopolysaccharide Receptors; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D017452:Receptors, IgG / Q000032:analysis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000469:Alkaline Phosphatase