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Copyright ©ERS Journals Ltd 2006
Role of tumour necrosis factor-
receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema
11 Depts of Respiratory Diseases, and 2 Neurology, Ghent University Hospital, Ghent, Belgium.
CORRESPONDENCE: A. I. D'hulst, Dept of Respiratory Diseases, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. Fax: 32 92402341. E-mail: an.dhulst{at}UGent.be
Keywords: Chronic obstructive pulmonary disease, cigarette smoking, emphysema, inflammation, tumour necrosis factor-
receptors, weight loss
Received: May 19, 2005
Accepted February 27, 2006
Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-
To investigate the contribution of each TNF-
CS was found to significantly increase the protein levels of soluble TNF-
These current findings suggest that both tumour necrosis factor-
has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF- receptors. receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF- R1 knockout (KO) mice, TNF- R2 KO mice and wild type (WT) mice. R1 (by four-fold) and TNF- R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF- R1 KO mice. In TNF- R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF- R2 KO mice in contrast to WT and TNF- R1 KO mice. CS-exposed WT and TNF- R1 KO mice failed to gain weight, whereas the body mass of TNF- R2 KO mice was not affected. receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor- receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.
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