1. The role of β2 integrin associated heparin-binding protein release in ARDS
- Author
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Shouqin Zhang, Shaolin Ma, Xiangyu Zhang, Xuebin Wang, Yajing Feng, Yang Liu, and Sheng Wang
- Subjects
Male ,0301 basic medicine ,MAPK/ERK pathway ,ARDS ,Neutrophils ,p38 mitogen-activated protein kinases ,Integrin ,Pulmonary Edema ,Inflammation ,Lung injury ,Pharmacology ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,Cecum ,Ligation ,Cells, Cultured ,Respiratory Distress Syndrome ,medicine.diagnostic_test ,biology ,business.industry ,030208 emergency & critical care medicine ,Blood Proteins ,General Medicine ,Pulmonary edema ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Bronchoalveolar lavage ,CD18 Antigens ,biology.protein ,medicine.symptom ,Carrier Proteins ,business ,Bronchoalveolar Lavage Fluid ,Antimicrobial Cationic Peptides ,Signal Transduction - Abstract
Aims PMNs (polymorphonuclear neutrophil) play important roles in early stage of inflammation induced ARDS (Acute Respiratory Distress Syndrome). Both HBP (Heparin-Binding Protein) released from active PMNs and β2 integrins on the surface of PMNs are involved in vascular leakage. The role and relationship of HBP and β2 integrins on ARDS still requires study. Materials and methods We established ARDS model using C57BL/6 mice with cecal ligation and puncture and eliminating HBP and β2 integrin with respective antibodies. The mice were also challenged with HBP endotracheal instillation. Histopathology score, lung wet/dry ratio, bronchoalveolar lavage fluid protein, plasma HBP and β2 integrin on PMNs from all groups were measured. β2 integrin and HBP were analyzed after incubated PMNs with streptococcal and pretreat with anti-CD18, anti-HBP, 1-phosphatidylinositol 3-kinase (PI3K) inhibitor and p38 mitogen-activated protein kinase (MAPK) inhibitor. Key findings All lung injury indicatrix accompanied with HBP and β2 integrin elevated in CLP group, and HBP and β2 integrin were in correlation with each other and both were in correlation with the severity of lung injury. Endotracheal instillation HBP induced lung injury in CLP mice. Inhibiting both HBP and integrin ameliorated lung injury. HBP release was suppressed by inhibiting integrin and PI3K pathway, while integrin level did not decrease after eliminating HBP. Significance Both HBP and β2 integrin play important roles in ARDS. HBP released from PMNs is β2 integrin-PI3K signaling pathway dependent process revealing potential novel therapeutic targets for ARDS treatment.
- Published
- 2018
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