Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Abstract

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha 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-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha 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.

• Authors: A I D'hulst, K R Bracke, T Maes, J L De Bleecker, R A Pauwels, G F Joos, G G Brusselle
• Journal: The European respiratory journal (Eur Respir J) Vol. 28 Issue 1 Pg. 102-12 (Jul 2006) ISSN: 0903-1936 [Print] England
• PMID: 16540505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Tumor Necrosis Factor, Type II
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Apoptosis
• Body Weight
• Bronchoalveolar Lavage
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Humans
• Mice
• Mice, Knockout
• Pneumonia (metabolism, pathology)
• Pulmonary Emphysema (metabolism, pathology)
• Receptors, Tumor Necrosis Factor, Type II (metabolism, physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Smoking
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)