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Role of lymphotoxin-alpha in cigarette smoke-induced inflammation and lymphoid neogenesis
- Source :
- Europe PubMed Central, EUROPEAN RESPIRATORY JOURNAL, The European Respiratory Journal, Vol. 34, no. 2, p. 405-416 (2009)
- Publication Year :
- 2009
-
Abstract
- In chronic obstructive pulmonary disease (COPD), chronic inflammation is accompanied by peribronchial lymphoid aggregates. Lymphotoxin (LT)-alpha, crucial in secondary lymphoid organogenesis, may be involved in lymphoid neogenesis. We examined cigarette smoke (CS)-induced pulmonary lymphoid neogenesis and inflammation in vivo in LT alpha knockout (LT alpha(-/-)) and wild-type (WT) mice and studied the expression of lymphoid chemokines by lung fibroblasts in vitro. T-cell numbers (in bronchoalveolar lavage fluid (BALF) and lungs) and lymphoid aggregate numbers were significantly higher in air-exposed LT alpha(-/-) mice than in WT animals, and increased upon chronic CS exposure in both genotypes. In contrast, local immunoglobulin A responses upon chronic CS exposure were attenuated in LT alpha(-/-) mice. CXC chemokine ligand (CXCL) 13 and CC chemokine ligand (CCL) 19 mRNA in total lung and CXCL13 protein level in BALF increased upon CS exposure in WT, but not in LT alpha(-/-) mice. In vitro lymphotoxin-beta receptor (LT beta R) stimulation induced CXCL13 and CCL19 mRNA in WT lung fibroblasts. Furthermore, in vitro exposure to CS extract upregulated CXCL13 mRNA expression in WT, but not in LT beta R-/-, lung fibroblasts. In this murine model of COPD, CS induces pulmonary expression of lymphoid chemokines CXCL13 and CCL19 in a LT alpha beta-LT beta R-dependent fashion. However, LT alpha is not required for CS-induced pulmonary lymphocyte accumulation and neogenesis of lymphoid aggregates.
- Subjects :
- Pulmonary and Respiratory Medicine
Lymphotoxin alpha
Lymphotoxin-beta
Male
Lymphoid Tissue
medicine.medical_treatment
cigarette smoking
Alpha (ethology)
cytokines and chemokines
Neogenesis
Mice
Pulmonary Disease, Chronic Obstructive
Lymphotoxin beta Receptor
Smoke
medicine
Animals
mouse models
CXCL13
Lung
Lymphotoxin-alpha
Inflammation
Mice, Knockout
medicine.diagnostic_test
biology
business.industry
Chronic obstructive pulmonary disease
CCL19
Smoking
Fibroblasts
biology.organism_classification
Molecular biology
Chemokine CXCL13
respiratory tract diseases
Mice, Inbred C57BL
Bronchoalveolar lavage
Cytokine
Lymphotoxin
Immunology
Chemokine CCL19
lymphotoxin-alpha
business
Bronchoalveolar Lavage Fluid
Subjects
Details
- ISSN :
- 13993003 and 09031936
- Volume :
- 34
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The European respiratory journal
- Accession number :
- edsair.doi.dedup.....9040d2a03d1cd046b381943e34237825