Recombinant granulocyte colony-stimulating factor induces production of human neutrophil peptides in lung cancer patients with neutropenia.
Human neutrophil peptides (HNPs) 1, 2 and 3 are antimicrobial peptides localized in the azurophil granules of neutrophils. We investigated the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the biosynthesis of HNPs 1-3 using a sensitive radioimmunoassay and Northern blot analysis. Seven patients with lung cancer were first treated with various anticancer agents for 3 days (days 1-3) followed by treatment with rhG-CSF (2 microgram/kg weight/day) for 7 days (days 8-14). Chemotherapy caused neutropenia but the neutrophil count increased biphasically between days 8 and 14. Chemotherapy did not change the baseline plasma concentration of HNPs 1-3 (74.1+/-2.1 pmol/ml) but the concentration increased from day 12, 5 days after commencement of rhG-CSF therapy, to reach a peak value of 430.8+/-57.0 pmol/ml on day 15, 1 day after the last administration of rhG-CSF. Baseline HNPs 1-3 content per neutrophil was 0.59+/-0.02 fmol, decreased to 0.30+/-0.07 fmol on day 9, then increased to 0.78+/-0.07 fmol on day 15. Analyses of peripheral blood neutrophils by Northern blot and reverse-phase high-performance liquid chromatography showed that the amounts of HNPs 1-3 mRNA and precursors of HNPs 1-3 markedly increased in response to rhG-CSF. Our results indicate that recombinant hG-CSF does not only increase neutrophil count but stimulates HNPs 1-3 biosynthesis in neutrophils, thus enhancing the host defense system of compromised hosts with neutropenia.
Ashitani
J
J
Third Department of Internal Medicine, Miyazaki Medical College, Kihara 5200, Kiyotake, 889-1692, Miyazaki, Japan.
Nakazato
M
M
Mukae
H
H
Taniguchi
H
H
Date
Y
Y
Matsukura
S
S
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D000368:Aged; D000890:Anti-Infective Agents / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D018288:Carcinoma, Small Cell / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D023082:Defensins / Q000097:blood* / Q000235:genetics*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins; D023084:alpha-Defensins
D000890:Anti-Infective Agents; D023082:Defensins; D011994:Recombinant Proteins; D023084:alpha-Defensins; C406564:defensin NP-1; D016179:Granulocyte Colony-Stimulating Factor