Role of TNF receptor 2 in cigarette smoke-induced pulmonary inflammation and emphysema

¹ Dept of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium
² Dept of Neurology, Ghent University Hospital, Ghent, Belgium

^* To whom correspondence should be addressed. E-mail: an.dhulst{at}UGent.be.

	Abstract

Chronic Obstructive Pulmonary Disease (COPD) is characterized by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. tumour Necrosis Factor- (TNF) has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 TNF receptor (R2). To investigate the contribution of each TNF receptor in the pathogenesis of COPD, we studied the effects of chronic air or cigarette smoke (CS)-exposure in TNF R1 KO, TNF R2 KO and WT. CS significantly increased the protein levels of soluble TNF R1 (4-fold) and TNF R2 (10-fold) in BAL of WT. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF R1 KO. In TNF R2 KO, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF R2 KO in contrast to WT and TNF R1 KO. CS-exposed WT and TNF R1 KO failed to gain weight, whereas body mass of TNF R2 KO was not affected. These findings suggest that both TNF receptors contribute to the pathogenesis of COPD, but TNF R2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of COPD.

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