Granulocyte function is stimulated by a novel hexapeptide, WKYMVm, in chemotherapy-treated cancer patients.
Bacterial infections are major life-threatening complications in patients receiving cytotoxic drugs. These infections generally occur during periods of neutropenia. It has been suggested that the incidence of neutropenia correlates with the incidence of infections. A synthetic hexapeptide, WKYMVm, which stimulates phosphoinositide hydrolysis in leukocytes, has been shown to activate microbicidal activities of human polymorphonuclear neutrophils. In this study, we evaluate whether WKYMVm stimulates bactericidal activity in neutrophils obtained from patients who received chemotherapy for solid tumors when they were neutropenic. Eight patients and 11 healthy controls were recruited for the study. Patient neutrophils, on day 0 and at 2 weeks after chemotherapy, were collected. Expression of the WKYMVm peptide receptor, on leukocytes, was analyzed by fluorescein-activated cell sorting. Neutrophil bactericidal assays were performed using both reactive oxygen species generation and intracellular killing. Expression of the WKYMVm peptide receptor on leukocytes showed no difference in the treated patients compared to healthy controls. WKYMVm increased bactericidal activities, in a dose-dependent fashion, of control neutrophils compared to treated patient neutrophils obtained on day 0. WKYMVm markedly stimulated bactericidal activity of treated patient neutrophils obtained at 2 weeks after chemotherapy compared to treated patient neutrophils obtained on day 0. WKYMVm augmented neutrophil bactericidal activity was noted at low concentration but was suppressed at higher concentrations of 5-fluorouracil. WKYMVm augmented neutrophil bactericidal activity was not suppressed by cisplatin. WKYMVm has the potential for increasing neutrophil bactericidal activity in chemotherapy-treated cancer patients.
Division of Hematology-Oncology; Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Korea.
Hawk
H
Kim
Jae Hoo
JH
Park
Eun-Hee
EH
Lee
Mee-Ja
MJ
Kim
Sang Kyu
SK
Park
Sook-Kyoung
SK
Heo
Byung-Sam
BS
Kim
Young Joo
YJ
Min
D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001770:Blood Bactericidal Activity / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009503:Neutropenia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000378:metabolism
D009842:Oligopeptides; D011956:Receptors, Cell Surface; C113617:Trp-Lys-Tyr-Met-Val-Met; D002945:Cisplatin; D005472:Fluorouracil