Effect of granulocyte-colony stimulating factor on generation of oxygen-derived free radicals and myeloperoxidase activity in neutrophils from poorly controlled NIDDM patients.
To evaluate whether granulocyte-colony stimulating factor (G-CSF) improves an impaired production of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients, we studied the effect of G-CSF on myeloperoxidase (MPO) activity and chemiluminescence amplified by a Cypridina luciferin analog (CLA-DCL), which is dependent on O2 generation, and luminol (L-DCL), which is dependent on OCl(-) generation, in response to formyl-methonyl-leucyl-phenylalanine. Both CLA-DCL and L-DCL by neutrophils from the diabetic group (n = 15, HbA(1c) >10%) were significantly decreased (26 and 37%, respectively: P < 0.01) compared with the age-matched normal control group (n = 15), and L-DCL was more sensitive to this inhibition than CLA-DCL (P < 0.05). In both control and diabetic neutrophils, G-CSF significantly enhanced both CLA-DCL (175% in control and 156% in diabetic) and L-DCL (283% in control and 346% in diabetic). In diabetic neutrophils, the enhancing effect of G-CSF on L-DCL was more sensitive than on CLA-DCL (P < 0.001). There was a positive correlation between HbA(1c) and the enhancing effect of G-CSF on L-DCL in diabetic patients (P < 0.05), but not on CLA-DCL. MPO activity was also decreased in the diabetic group (63%, P < 0.05), and G-CSF improved this impaired MPO activity (184%, P < 0.01). Furthermore, there was a positive correlation between HbA(1c) and the improving effect of G-CSF on MPO activity (P < 0.05). Because bacterial infection still accounts for an important cause of morbidity and mortality in diabetic patients, these data suggest that G-CSF may be useful as a drug to prevent the aggravation of bacterial infection by improving neutrophil function, especially through H2O2-MPO-OCl(-) mechanism, in poorly controlled diabetic patients.
Sato
N
N
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Kashima
K
K
Tanaka
Y
Y
Shimizu
H
H
Mori
M
M
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000201:enzymology; D049454:Firefly Luciferin; D006442:Glycated Hemoglobin / Q000032:analysis*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D009195:Peroxidase / Q000097:blood*; D011994:Recombinant Proteins; D012016:Reference Values; D012044:Regression Analysis; D013481:Superoxides / Q000097:blood*
D001786:Blood Glucose; D049454:Firefly Luciferin; D006442:Glycated Hemoglobin; D016179:Granulocyte Colony-Stimulating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010100:Oxygen; D009195:Peroxidase; D011994:Recombinant Proteins; D013481:Superoxides