Stimulation of the adherence of Haemophilus influenzae to human lung epithelial cells by antimicrobial neutrophil defensins.
Patients with chronic obstructive pulmonary disease (COPD) frequently have recurrent lower respiratory tract infections with nonencapsulated Haemophilus influenzae. The infected mucosa of these patients is infiltrated with neutrophils, which upon activation may release antimicrobial peptides, including defensins. It was shown that defensins isolated from neutrophils or from sputum samples of COPD patients did not kill H. influenzae from these patients, but they did stimulate its adherence to human bronchial epithelial cells in a time- and dose-dependent manner. Maximal stimulation was observed after 3 h in the presence of > or = 10 micrograms/mL defensins, resulting in 65 +/- 36 cfu/cell (61-fold increase). The enhanced adherence was not solely due to charge effects and was specifically blocked by alpha 1-proteinase inhibitor. Because adherence is the first step in the onset of respiratory tract infections, our findings indicate that neutrophil defensins likely contribute to the pathogenesis of H. influenzae infection in the lower respiratory tract.
Gorter
A D
AD
Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands. Annelies.Gorter@RIVM.NL
Eijk
P P
PP
van Wetering
S
S
Hiemstra
P S
PS
Dankert
J
J
van Alphen
L
L
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001422:Bacterial Adhesion; D016667:Bacterial Capsules; D023082:Defensins; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000382:microbiology / Q000648:ultrastructure; D006192:Haemophilus Infections / Q000209:etiology; D006193:Haemophilus influenzae / Q000472:pathogenicity* / Q000648:ultrastructure; D006801:Humans; D008168:Lung / Q000382:microbiology* / Q000648:ultrastructure; D008173:Lung Diseases, Obstructive / Q000276:immunology* / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology*; D011506:Proteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D023082:Defensins; D011506:Proteins