Acyl homoserine lactones induce early response in the airway.
Acyl homoserine lactones (AHLs) are intercellular signaling molecules used in quorum sensing by Gram-negative bacteria. We studied the early effects on the rat airway of in vivo intratracheal administration of AHLs (i.e., P. aeruginosa and B. cepacia) to test the hypothesis that AHLs also act on the airway cells, modifying secretory mechanisms which are important in mucosal defense. One hour after treatment, N-butyryl-homoserine lactone (C4-HL) had caused dilated extracellular spaces, loss of cilia, reduction of secretory material, and the presence of pre-necrotic elements in the epithelium, while N-octanoyl-homoserine lactone (C8-HL) caused a mild lesion in the epithelium. After treatment with either C4- or C8-HL, reduced immunoreactivity was found using CC10 antibody. At ultrastructural examination, dilatation of the mitochondria was evident in ciliate and secretory cells, while solitary chemosensory cells appeared better preserved, showing aspects of nucleocytoplasmic activation. Using microarray analysis, we found down-regulation of early gene Fos and Egr1 in all AHL-treated specimens. In vivo pharmacological magnetic resonance imaging after C4- or C8-HL treatment showed a slight increase in tracheal secretion at a first evaluation 5 min after administration, with no increase in the following minutes. In conclusion, AHLs induce an early mucosal response, and the chondriomas of ciliate and secretory cells are the main cytological target of AHL action. Our results show that AHL action is not limited to activation of conspecific bacteria, but also modifies innate airway defense mechanisms.
Sbarbati
Andrea
A
Department of Morphological-Biomedical Sciences, Section of Human Anatomy and Histology, University of Verona, Verona, Italy.
Tizzano
Marco
M
Merigo
Flavia
F
Benati
Donatella
D
Nicolato
Elena
E
Boschi
Federico
F
Cecchini
Maria Paola
MP
Scambi
Ilaria
I
Osculati
Francesco
F
D054742:Acyl-Butyrolactones / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging; D051381:Rats; D017208:Rats, Wistar; D012137:Respiratory System / Q000187:drug effects* / Q000648:ultrastructure; D014158:Transcription, Genetic / Q000187:drug effects*
D054742:Acyl-Butyrolactones; D015415:Biomarkers