Lipopolysaccharide tolerance in relation to intrabronchial influx of neutrophils in the rat

Citation
M. Shimada et al., Lipopolysaccharide tolerance in relation to intrabronchial influx of neutrophils in the rat, LUNG, 178(4), 2000, pp. 235-248
Citations number
32
Categorie Soggetti
Cardiovascular & Respiratory Systems","da verificare
Journal title
LUNG
ISSN journal
03412040 → ACNP
Volume
178
Issue
4
Year of publication
2000
Pages
235 - 248
Database
ISI
SICI code
0341-2040(200007/08)178:4<235:LTIRTI>2.0.ZU;2-X
Abstract
Lipopolysaccharide (LPS) is a potent chemotactic component for polymorphonu clear leukocytes (PMN, neutrophils). Since LPS tolerance was first describe d, many studies have been reported about the hyporesponsiveness bl vitro co rresponding to attenuating: production of proinflammatory cytokines. We hypothesized that in vivo daily exposure to LPS stimuli impairs neutroph il accumulation in the rat airway. Interleukin 8 (IL-8) and/or CXC-chemokin e, a neutrophil chemoattractant and activating cytokine, have been implicat ed as proinflammatory mediators in gram-negative respiratory tract infectio ns. It is possible that the tolerance to LPS has occurred in relation to th is chemoattractant cytokine production. To settle this issue, we examined whether the neutrophil count in bronchoal veolar lavage fluid (BALF) decreases after daily inhalation of Pseudomonas aeruginosa LPS into the rat airway. Repeated inhalation of LPS into the airway resulted in reduction in neutrop hil recruitment. We measured rat CXC-chemokine (rat GRO/CINC1) levels in re covered BALF. There were noted reductions of rat GRO corresponding to the d iminished neutrophil trafficking. We also confirmed that the HLA DR positiv e lymphocyte number in BALF gradually increased after daily inhalation of L PS. These results suggest that continuous stimuli of LPS mitigate the accumulat ion of inflammatory cells in the airway by reducing chemokine production wi th a consequent change in the appearance of local inflammation to a chronic state.