Proceedings of The Physiological Society

Kings College London (2005) J Physiol 565P, C168

Communications

Lipopolysaccharide-induced inflammation of the carotid body: Histopathology and factors involved

Fernandez, R ; Gonzalez, S ; Cortes, P P; Maisey, K ; Reyes, E P; Zapata, P ;

1. Lab. Neurobiology, P. Catholic University of Chile, Santiago, Chile. 2. Dept. Pathology, P. Catholic University of Chile, Santiago, Chile. 3. Dept. Biology, University of Santiago of Chile, Santiago, Chile.


Carotid body (CB) inflammation was induced by lipopolysaccharide (LPS) either applied topically or infused i.v. Experiments were performed in 26 adults cats anaesthetized with sodium pentobarbitone 40 mg/kg I.P., supplemented I.V. as required, and whose body temperature was maintained at 38oC by a regulated heating pad. Cats breathed spontaneously through a tracheal cannula. CBs were excised 5 h after LPS administration, paraffin-embedded, cut into 5 μm sections and stained with haematoxylin-eosin. Cats were euthanized by an overdose of pentobarbitone given I.V. at the end of experiments. Single or repeated topical applications of 2 μg LPS to CB surface increased the number of polymorphonuclear (PMN) leukocytes infiltrating CB vasculature and stroma (n=10). LPS infused I.V. (750 μg/kg at 0.35 ml/min along 20 min) markedly disorganized CB cell clusters, increasing the number of PMN cells mainly in the vascular bed, and collagen and fibrin deposition (n=11). Functional manifestations of CB inflammation are presented in a separate communication (Zapata et al). That the reduction in CB chemoreceptor activity and ventilatory chemoreflexes reported there is not due to glomus cells death, was indicated by TUNEL (terminal deoxy-nucleotidyl transferase-mediated deoxyuridinetriphosphate nick end labeling) assays. This leads to the proposal that soluble pro-inflammatory mediators may diminish CB chemosensory activity. Since I.V. LPS increases plasma levels of tumour necrosis factor-α (TNF-α) in cats (Otto & Rawlings, 1995), we tested the hypothesis that TNF-α would affect CB chemosensory activity. This was done in carotid bifurcations (n=5) simultaneously perfused and superfused in vitro with Tyrode solution (pH 7.43 at 37.5°C), containing 5% CO2; the frequency of chemosensory discharges (fχ) was recorded from the whole carotid sinus nerve. TNF-α (0.2 pg-10 ng) bolus injections through the perfusion line (flowing at 2-3 ml/min) failed to evoke changes in basal fχ recorded during normoxia (PO2 110 Torr), but when applied upon a hypoxic background (PO2 30 Torr), TNF-α evoked a dose-dependent transient fall in the increased levels of fχ observed in that condition. RT-PCR studies performed on contralateral CBs determined that they express the mRNAs for both type I and type II TNF-α receptors. Our results support the idea that TNF-α-induced changes in CB chemosensory activity observed in vitro may participate in the depression of chemoreceptor activity and ventilatory chemoreflexes induced by LPS in the entire animal. In addition, these results suggest that the CB may serve as a cytokine chemoreceptor for sensing immune signals.

Where applicable, experiments conform with Society ethical requirements