Peptidoglycan Recognition Protein 1 Promotes House Dust Mite–Induced Airway Inflammation in Mice
| Autor: | Meixia Gao, Zu-Xi Yu, Xuan Qu, Katharine S. Meyer, Xianglan Yao, Jichun Chen, Cuilian Dai, Stewart J. Levine, Pradeep K. Dagur, Gayle Z. Nugent, Karen J. Keeran, J. Philip McCoy |
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| Rok vydání: | 2013 |
| Předmět: |
Pulmonary and Respiratory Medicine
Chemokine Dermatophagoides pteronyssinus Clinical Biochemistry Biology Mice Th2 Cells Antigen Macrophages Alveolar medicine Animals CCL17 Antigens Dermatophagoides Lung Molecular Biology Mice Knockout Mice Inbred BALB C Transplantation Chimera Innate immune system medicine.diagnostic_test Articles Cell Biology Allergens respiratory system Asthma Immunity Innate Up-Regulation respiratory tract diseases Eosinophils Disease Models Animal Bronchoalveolar lavage Chemokines CC Immunology Peptidoglycan recognition protein 1 biology.protein Cytokines CCL24 CCL22 |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 49:902-911 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/rcmb.2013-0001oc |
| Popis: | Peptidoglycan recognition protein (Pglyrp) 1 is a pattern-recognition protein that mediates antibacterial host defense. Because we had previously shown that Pglyrp1 expression is increased in the lungs of house dust mite (HDM)-challenged mice, we hypothesized that it might modulate the pathogenesis of asthma. Wild-type and Pglyrp1(-/-) mice on a BALB/c background received intranasal HDM or saline, 5 days/week for 3 weeks. HDM-challenged Pglyrp1(-/-) mice showed decreases in bronchoalveolar lavage fluid eosinophils and lymphocytes, serum IgE, and mucous cell metaplasia, whereas airway hyperresponsiveness was not changed when compared with wild-type mice. T helper type 2 (Th2) cytokines were reduced in the lungs of HDM-challenged Pglyrp1(-/-) mice, which reflected a decreased number of CD4(+) Th2 cells. There was also a reduction in C-C chemokines in bronchoalveolar lavage fluid and lung homogenates from HDM-challenged Pglyrp1(-/-) mice. Furthermore, secretion of CCL17, CCL22, and CCL24 by alveolar macrophages from HDM-challenged Pglyrp1(-/-) mice was markedly reduced. As both inflammatory cells and airway epithelial cells express Pglyrp1, bone marrow transplantation was performed to generate chimeric mice and assess which cell type promotes HDM-induced airway inflammation. Chimeric mice lacking Pglyrp1 on hematopoietic cells, not structural cells, showed a reduction in HDM-induced eosinophilic and lymphocytic airway inflammation. We conclude that Pglyrp1 expressed by hematopoietic cells, such as alveolar macrophages, mediates HDM-induced airway inflammation by up-regulating the production of C-C chemokines that recruit eosinophils and Th2 cells to the lung. This identifies a new family of innate immune response proteins that promotes HDM-induced airway inflammation in asthma. |
| Databáze: | OpenAIRE |
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