Lipopolysaccharide-induced carotid body inflammation in cats: Functional manifestations, histopathology and involvement of tumour necrosis factor-?
Keywords: model, apoptosis, localization, endothelium, animals, expression, lipopolysaccharide, movement, transcription, chemoreceptor, inflammation, blood, protein, cell, hypoxia, disease, chain, histopathology, alpha, immunohistochemistry, tumor, experiment, male, receptor, polymerase, cat, vitro, electrophysiology, hematocrit, tissue, body, necrosis, factor-alpha, neutrophils, reflex, article, factor, tachycardia, ventilation, hypotension, cats, pulmonary, vessel, type, controlled, animal, reverse, endotoxemia, study, 1, carotid, Reaction, in, nonhuman, Receptors,, RNA,, 2, Messenger, I, Models,, Lipopolysaccharides, tachypnea, ii, Factor,, pentobarbital, neuritis
In the absence of information on functional manifestations of carotid body (CB) inflammation, we studied an experimental model in which lipopolysaccharide (LPS) administration to pentobarbitone-anaesthetized cats was performed by topical application upon the CB surface or by intravenous infusion (endotoxaemia). The latter caused: (i) disorganization of CB glomoids, increased connective tissue, and rapid recruitment of polymorphonuclear cells into the vascular bed and parenchyma within 4 h; (ii) increased respiratory frequency and diminished ventilatory chemoreflex responses to brief hypoxia (breathing 100% N 2 for 10 s) and diminished ventilatory chemosensory drive (assessed by 100% O 2 tests) during normoxia and hypoxia; (iii) tachycardia, increased haematocrit and systemic hypotension in response to LPS i.v.; and (iv) increased basal frequency of carotid chemosensory discharges during normoxia, but no change in maximal chemoreceptor responses to brief hypoxic exposures. Lipopolysaccharide-induced tachypnoea was prevented by prior bilateral carotid neurotomy. Apoptosis was not observed in CBs from cats subjected to endotoxaemia. Searching for pro-inflammatory mediators, tumour necrosis factor-? (TNF-?) was localized by immunohistochemistry in glomus and endothelial cells; reverse transcriptase-polymerase chain reaction revealed that the CB expresses the mRNAs for both type-1 (TNF-R1) and type-2 TNF-? receptors (TNF-R2); Western blot confirmed a band of the size expected for TNF-R1; and histochemistry showed the presence of TNF-R1 in glomus cells and of TNF-R2 in endothelial cells. Experiments in vitro showed that the frequency of carotid nerve discharges recorded from CBs perfused and superfused under normoxic conditions was not significantly modified by TNF-?, but that the enhanced frequency of chemosensory discharges recorded along responses to hypoxic stimulation was transiently diminished in a dose-dependent manner by TNF-? injections. The results suggest that the CB may operate as a sensor for immune signals, that the CB exhibits histological features of acute inflammation induced by LPS, that TNF-? may participate in LPS-induced changes in chemosensory activity and that some pathophysiological reactions to high levels of LPS in the bloodstream may originate from changes in CB function. © 2008 The Authors.
|Título de la Revista:||Experimental Physiology|
|Editorial:||The Physiological Society, Wiley-Blackwell|
|Fecha de publicación:||2008|
|Página de inicio:||892|