gC1qR Antibody Can Modulate Endothelial Cell Permeability in Angioedema
| العنوان: | gC1qR Antibody Can Modulate Endothelial Cell Permeability in Angioedema |
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| المؤلفون: | Allen P. Kaplan, Marina Fandaros, Berhane Ghebrehiwet, Kusumam Joseph, David A. Rubenstein, Wei Yin |
| المصدر: | Inflammation. 45:116-128 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | High-molecular-weight kininogen, Immunology, Bradykinin, Vascular permeability, Cell morphology, Permeability, Capillary Permeability, Mitochondrial Proteins, Classical complement pathway, chemistry.chemical_compound, Humans, Immunology and Allergy, Angioedema, Receptor, biology, Chemistry, Antibodies, Monoclonal, Endothelial Cells, Cardiovascular Agents, Molecular biology, Endothelial stem cell, biology.protein, Endothelium, Vascular, Antibody, Carrier Proteins, Shear Strength, Biomarkers |
| الوصف: | Angioedema is characterized by swelling of the skin or mucous membranes. Overproduction of the vasodilator bradykinin (BK) is an important contributor to the disease pathology, which causes rapid increase in vascular permeability. BK formation on endothelial cells results from high molecular weight kininogen (HK) interacting with gC1qR, the receptor for the globular heads of C1q, the first component of the classical pathway of complement. Endothelial cells are sensitive to blood-flow-induced shear stress and it has been shown that shear stress can modulate gC1qR expression. This study aimed to determine the following: (1) how BK or angioedema patients' (HAE) plasma affected endothelial cell permeability and gC1qR expression under shear stress, and (2) if monoclonal antibody (mAb) 74.5.2, which recognizes the HK binding site on gC1qR, had an inhibitory effect in HK binding to endothelial cells. Human dermal microvascular endothelial cells (HDMECs) grown on Transwell inserts were exposed to shear stress in the presence of HAE patients' plasma. Endothelial cell permeability was measured using FITC-conjugated bovine serum albumin. gC1qR expression and HK binding to endothelial cell surface was measured using solid-phase ELISA. Cell morphology was quantified using immunofluorescence microscopy. The results demonstrated that BK at 1 µg/mL, but not HAE patients' plasma and/or shear stress, caused significant increases in HDMEC permeability. The mAb 74.5.2 could effectively inhibit HK binding to recombinant gC1qR, and reduce HAE patients' plasma-induced HDMEC permeability change. These results suggested that monoclonal antibody to gC1qR, i.e., 74.5.2, could be potentially used as an effective therapeutic reagent to prevent angioedema. |
| تدمد: | 1573-2576 0360-3997 |
| DOI: | 10.1007/s10753-021-01532-w |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8a9b4dd202d61afb596bf47b332b93a https://doi.org/10.1007/s10753-021-01532-w |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....e8a9b4dd202d61afb596bf47b332b93a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15732576 03603997 |
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| DOI: | 10.1007/s10753-021-01532-w |