Human neutrophil defensins induce lung epithelial cell proliferation in vitro.
Repair of injured airway epithelium is often accompanied by an influx of leukocytes, and these cells have been suggested to contribute to the repair process. The aim of the present study was to investigate the effect of neutrophil defensins--antimicrobial peptides present in large amounts in the neutrophil--on proliferation of cultured lung epithelial cells. Neutrophil defensins at 4-10 microg/ml enhanced proliferation of the A549 lung epithelial cell line as assessed using cell counting, BrdU incorporation, and the tetrazolium salt MTT assay. Higher, cytotoxic concentrations of defensins decreased cell proliferation. Whereas defensin-induced cell proliferation was not inhibited by the EGF receptor tyrosine kinase inhibitor AG1478, it was completely inhibited by the mitogen-activated protein (MAP) kinase kinase (MEK) inhibitor U0126, suggesting that defensins mediate cell proliferation via an EGF receptor-independent, MAP kinase signaling pathway. Although the cytotoxic effect of defensins was inhibited by alpha1-proteinase inhibitor, the defensin-induced cell proliferation was not affected. These data suggest that neutrophil defensins may possibly be involved in epithelial repair in the airways by inducing lung epithelial cell proliferation.
Aarbiou
Jamil
J
Departments of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. j.aarbiou@lumc.nl
Ertmann
Marloes
M
van Wetering
Sandra
S
van Noort
Peter
P
Rook
Denise
D
Rabe
Klaus F
KF
Litvinov
Sergey V
SV
van Krieken
J Han J M
JH
de Boer
Willem I
WI
Hiemstra
Pieter S
PS
D002455:Cell Division / Q000187:drug effects; D023082:Defensins / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000166:cytology*; D020935:MAP Kinase Signaling System; D009504:Neutrophils / Q000737:chemistry; D020545:Respiratory Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D023082:Defensins; D006133:Growth Substances; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D066246:ErbB Receptors