T cell-derived TNF down-regulates acute airway response to endotoxin.
Acute and chronic airway inflammations caused by environmental agents including endotoxin represent an increasing health problem. Local TNF production may contribute to lung dysfunction and inflammation, although pulmonary neutrophil recruitment occurs in the absence of TNF. First, we demonstrate that membrane-bound TNF is sufficient to mediate the inflammatory responses to lipopolysaccharide (LPS). Secondly, using cell type-specific TNF-deficient mice we show that TNF derived from either macrophage/neutrophil (M/N) or T lymphocytes have differential effects on LPS-induced respiratory dysfunction (enhanced respiratory pause, Penh) and pulmonary neutrophil recruitment. While Penh, vascular leak, neutrophil recruitment, TNF, and thymus- and activation-regulated chemokine/CCL17 (TARC) expression in the lung were reduced in M/N-deficient mice, T cell-specific TNF-deficient mice displayed augmented Penh, vascular leak, neutrophil influx, increased CD11c+ cells and expression of TNF, TARC and murine CXC chemokines KC/CXCL1 in the lung. In conclusion, inactivation of TNF in either M/N or T cells has differential effects on LPS-induced lung disease, suggesting that selective deletion of TNF in T cells may aggravate airway pathology.
Togbe
Dieudonnée
D
Université d'Orléans and Centre National de la Recherche Scientifique, Molecular Immunology and Embryology, Orléans, France.
Grivennikov
Sergei I
SI
Noulin
Nicolas
N
Couillin
Isabelle
I
Maillet
Isabelle
I
Jacobs
Muazzam
M
Maret
Marielle
M
Fick
Lizette
L
Nedospasov
Sergei A
SA
Quesniaux
Valérie F J
VF
Schnyder
Bruno
B
Schnyder-Candrian
Silvia
S
D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology*; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010993:Plethysmography, Whole Body; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000502:physiology*
D004731:Endotoxins; D048069:Tumor Necrosis Factors