Tumor Necrosis Factor-a Receptor p55, but not p75, is Involved in Diesel Exhaust Particles- Induced Neutrophilic Pulmonary Inflammation

Background: Inhalation of diesel exhaust particles (DEP) induces an inflammatory reaction in the lung; however, the mechanisms are largely unclear. In our murine model of DEP-induced pulmonary inflammation, we observed increased Tumor Necrosis Factor (TNF)-a levels in bronchoalveolar lavage fluid (BALF). TNF-a signaling is crucial in several lung inflammatory responses and is mediated by binding of TNF-a with p55 (TNF-aR1) and p75 (TNF-aR2) receptors. Methods: To investigate the contribution of each TNF-a receptor in the pathogenesis of DEP-induced pulmonary inflammation, we examined the effects of intratracheal DEP instillation in TNF-aR1 knockout (KO) mice, TNF-aR2 KO mice, TNF-aR1R2 KO mice and wild type (WT) mice. Results: DEP exposure in WT mice induced a significant pulmonary inflammation with increased numbers of neutrophils and dendritic cells (DCs). In TNF-aR1 KO and TNF-aR1R2 KO mice, DEP-induced neutrophilic inflammation was significantly reduced whereas the number of DCs was similar as in WT mice. TNF-aR2 deficiency did not affect DEP-induced pulmonary inflammation. Percentage neutrophils (Mean ± SD) Saline DEP TNF-aR1 KO 0.5 ± 0.3 8.1 ± 2.3 *, † TNF-aR2 KO 0.8 ± 0.8 11.5 ± 2.5 * *: p