Antibacterial Defense of Human Airway Epithelial Cells from Chronic Obstructive Pulmonary Disease Patients Induced by Acute Exposure to Nontypeable Haemophilus influenzae: Modulation by Cigarette Smoke.
Antimicrobial proteins and peptides (AMPs) are a central component of the antibacterial activity of airway epithelial cells. It has been proposed that a decrease in antibacterial lung defense contributes to an increased susceptibility to microbial infection in smokers and patients with chronic obstructive pulmonary disease (COPD). However, whether reduced AMP expression in the epithelium contributes to this lower defense is largely unknown. We investigated the bacterial killing activity and expression of AMPs by air-liquid interface-cultured primary bronchial epithelial cells from COPD patients and non-COPD (ex-)smokers that were stimulated with nontypeable Haemophilus influenzae (NTHi). In addition, the effect of cigarette smoke on AMP expression and the activation of signaling pathways was determined. COPD cell cultures displayed reduced antibacterial activity, whereas smoke exposure suppressed the NTHi-induced expression of AMPs and further increased IL-8 expression in COPD and non-COPD cultures. Moreover, smoke exposure impaired NTHi-induced activation of NF-κB, but not MAP-kinase signaling. Our findings demonstrate that the antibacterial activity of cultured airway epithelial cells induced by acute bacterial exposure was reduced in COPD and suppressed by cigarette smoke, whereas inflammatory responses persisted. These findings help to explain the imbalance between protective antibacterial and destructive inflammatory innate immune responses in COPD.
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Gimano D
GD
Amatngalim
Jasmijn A
JA
Schrumpf
Almira
A
Henic
Esther
E
Dronkers
Renate M
RM
Verhoosel
Soledad R
SR
Ordonez
Henk P
HP
Haagsman
Maria E
ME
Fuentes
Sriram
S
Sridhar
Jamil
J
Aarbiou
Richard A J
RAJ
Janssen
Annemarie N
AN
Lekkerkerker
Pieter S
PS
Hiemstra
D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D001433:Bacteriolysis; D002478:Cells, Cultured; D000073865:Cigarette Smoking / Q000009:adverse effects*; D006192:Haemophilus Infections / Q000276:immunology*; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007109:Immunity; D056747:Immunomodulation; D016209:Interleukin-8 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology; D015398:Signal Transduction
D023181:Antimicrobial Cationic Peptides; D016209:Interleukin-8; D016328:NF-kappa B
Antimicrobial peptides; Chronic obstructive pulmonary disease; Cigarette smoke; Epithelium; Host defense