Leptin Modulates Innate and Adaptive Immune Cell Recruitment after Cigarette Smoke Exposure in Mice
Autor: | Nadja E. A. Drummen, Jan Tavernier, Juanita H. J. Vernooy, Guy Brusselle, Nele S. Pauwels, Robert-Jan van Suylen, Ken R. Bracke, Guy Joos, Emiel F.M. Wouters, Lennart Zabeau |
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Přispěvatelé: | Pulmonologie, RS: CAPHRI School for Public Health and Primary Care, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, RS: CARIM School for Cardiovascular Diseases |
Rok vydání: | 2010 |
Předmět: |
Leptin
Male EXPRESSION medicine.medical_specialty medicine.medical_treatment Immunology MOUSE-TISSUES Enzyme-Linked Immunosorbent Assay Respiratory Mucosa Adaptive Immunity OBSTRUCTIVE PULMONARY-DISEASE DENDRITIC CELLS GRAM-NEGATIVE PNEUMONIA Mice Pulmonary Disease Chronic Obstructive HOST-DEFENSE Immune system T-LYMPHOCYTES Internal medicine Animals Immunology and Allergy Medicine PNEUMOCOCCAL PNEUMONIA Mice Knockout Lung Leptin Deficiency medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction business.industry Pneumonia respiratory system Immunohistochemistry Immunity Innate Mice Inbred C57BL CXCL1 Chemotaxis Leukocyte Endocrinology Bronchoalveolar lavage medicine.anatomical_structure Cytokine DEFICIENT OB/OB MICE NEUROPEPTIDE-Y Receptors Leptin Tobacco Smoke Pollution business Bronchoalveolar Lavage Fluid CD8 |
Zdroj: | Journal of Immunology, 184(12), 7169-7177. American Association of Immunologists |
ISSN: | 1550-6606 0022-1767 |
Popis: | Leptin, a pleiotropic type I cytokine, was recently demonstrated to be expressed by resident lung cells in chronic obstructive pulmonary disease patients and asymptomatic smokers. To elucidate the functional role of leptin in the onset of chronic obstructive pulmonary disease, we tested leptin-deficient ob/ob mice (C57BL/6), leptin receptor-deficient db/db mice (C57BKS), and littermates in a model of cigarette smoke (CS)-induced pulmonary inflammation. Wild-type (WT) C57BL/6 mice were exposed for 4 or 24 wk to control air or CS. Pulmonary leptin expression was analyzed by immunohistochemistry and real-time PCR. Pulmonary inflammation upon 4 wk CS exposure was evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue of WT, ob/ob, and db/db mice. Immunohistochemical analysis revealed leptin expression in bronchial epithelial cells, pneumocytes, alveolar macrophages, and bronchial/vascular smooth muscle cells. The 4 and 24 wk CS exposure increased leptin expression in bronchial epithelial cells and pneumocytes versus air-exposed WT mice (p < 0.05). The 4 wk CS exposure resulted in increased accumulation of neutrophils, dendritic cells, macrophages, and lymphocytes in BALF and lung tissue of WT, ob/ob, and db/db mice. CS-exposed ob/ob and db/db mice showed in general higher numbers of neutrophils and lower numbers of CD4+, CD8+, and dendritic cells versus CS-exposed WT mice. Consistently, CXCL1 levels were enhanced in BALF of CS-exposed ob/ob and db/db mice versus WT mice (p < 0.05). Exogenous leptin administration completely restored the skewed inflammatory profile in ob/ob mice. These data reveal an important role of leptin in modulating innate and adaptive immunity after CS inhalation in mice. |
Databáze: | OpenAIRE |
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