Role of tumor endothelial marker 1 (Endosialin/CD248) lectin-like domain in lipopolysaccharide-induced macrophage activation and sepsis in mice
| Autor: | Yi Kai Hong, Chao Han Lai, Tsung Lin Cheng, Guey Yueh Shi, Hua Lin Wu, Yu Syuan Lin, Hung Wen Tsai, Chih Yuan Ma |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides medicine.medical_treatment Inflammation Mice Transgenic Lung injury Proinflammatory cytokine Sepsis 03 medical and health sciences Mice 0302 clinical medicine Antigens CD Antigens Neoplasm Physiology (medical) Lectins medicine Macrophage Animals Humans Mice Knockout Chemistry Monocyte Macrophages Biochemistry (medical) Public Health Environmental and Occupational Health General Medicine Macrophage Activation medicine.disease Recombinant Proteins Neoplasm Proteins Mice Inbred C57BL 030104 developmental biology Cytokine medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Tumor necrosis factor alpha medicine.symptom Gene Deletion |
| Zdroj: | Translational research : the journal of laboratory and clinical medicine. 232 |
| ISSN: | 1878-1810 |
| Popis: | Deleterious hyper-inflammation resulting from macrophage activation may aggravate sepsis and lead to lethality. Tumor endothelial marker 1 (TEM1), a type I transmembrane glycoprotein containing six functional domains, has been implicated in cancer and chronic sterile inflammatory disorders. However, the role of TEM1 in acute sepsis remains to be determined. Herein we explored the functional significance of the TEM1 lectin-like domain (TEM1D1) in monocyte/macrophage activation and sepsis using TEM1D1-deleted (TEM1LeD/LeD) transgenic mice and recombinant TEM1D1 (rTEM1D1) protein. Under stimulation with lipopolysaccharides (LPS) or several other toll-like receptor agonists, TEM1LeD/LeD macrophages produced lower levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 than wild-type TEM1wt/wt macrophages. Compared with TEM1wt/wt macrophages, LPS-macrophage binding and intracellular mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB activation were suppressed in TEM1LeD/LeD macrophages. In vivo, TEM1D1 deletion improved survival in LPS-challenged mice with reduction of circulating TNF-α and IL-6 and alleviation of lung injury and pulmonary leukocyte accumulation. In contrast, rTEM1D1 could bind to LPS and markedly suppress LPS-macrophage binding, MAPK/NF-κB signaling in macrophages and proinflammatory cytokine production. Treatment with rTEM1D1 improved survival and attenuated circulating TNF-α and IL-6, lung injury and pulmonary accumulation of leukocytes in LPS-challenged mice. These findings demonstrated differential roles for the TEM1 lectin-like domain in macrophages and soluble TEM1 lectin-like domain in sepsis. TEM1 in macrophages mediates LPS-induced inflammation via its lectin-like domain, whereas rTEM1D1 interferes with LPS-induced macrophage activation and sepsis. |
| Databáze: | OpenAIRE |
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