Altered function and surface marker expression of neutrophils induced by rhG-CSF treatment in severe congenital neutropenia.
Neutrophils from patients suffering from severe congenital neutropenia (SCN), who were receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF), were investigated in order to analyze the previously described decrease in chemotaxis. This study demonstrated the decreased chemotaxis to five well-known chemoattractants, FMLP, C5a, IL-8, LTB4 and PAF. To further investigate this impairment of patients' neutrophils, receptors and receptor turnover for chemoattractants were examined using flow cytometry. We found 1) increased FMLP receptor and decreased C5a receptor expression, 2) a normal expression of intracellular FMLP receptors after incubation with PMA, 3) increased loss and decreased re-expression of FMLP receptors after incubation with this peptide, 4) normal expression of adhesion glycoproteins CR3 (CD11b/CD18) and LFA1 (CD11a/CD18), 5) further signs of in vivo preactivation: high expression of Fc gamma-RI (CD64) and Fc gamma-RII (CD32), decreased expression of Fc gamma-RIII (CD16), increased expression of CD14, and low expression of HLA-DR. These data demonstrate that the decrease of chemotaxis of neutrophils from SCN patients is not due: a) to a decrease in the number of intra- or extracellular FMLP receptors; b) to a decrease of adhesion molecules. However, the decreased chemotaxis could result from an altered FMLP receptor turnover. The relevance of the altered Fc gamma-receptor pattern for the in vivo occurrence of side-effects, e.g. the necrotic vasculitis, of G-CSF treatment is discussed.
Fraunhofer Institute ITA, Department of Immunobiology, Hannover, FRG.
J
J
Elsner
J
J
Roesler
A
A
Emmendörffer
C
C
Zeidler
M L
ML
Lohmann-Matthes
K
K
Welte
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000187:drug effects / Q000378:metabolism; D000954:Antigens, Surface / Q000032:analysis; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015936:Complement C5a / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009503:Neutropenia / Q000097:blood* / Q000151:congenital / Q000188:drug therapy; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011961:Receptors, Fc / Q000187:drug effects / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D017452:Receptors, IgG; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D006684:HLA-DR Antigens; D007074:Immunoglobulin G; D016209:Interleukin-8; D011961:Receptors, Fc; D044042:Receptors, Formyl Peptide; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D016650:Fluorescein-5-isothiocyanate; D013755:Tetradecanoylphorbol Acetate