Reduction of endoglin receptor impairs mononuclear cell-migration
Aim: To test if the impairment of mononuclear cell (MNC) migration in patients with hereditary hemorrhagic telangiectasia (HHT) is due to the reduction of the endoglin (ENG) receptor on the cell surface and oxidative stress. Methods: MNCs of HHT patients and normal controls were subjected to migrat...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Open Exploration Publishing Inc.
2020-06-01
|
| Series: | Exploration of Medicine |
| Subjects: | |
| Online Access: | https://www.explorationpub.com/Journals/em/Article/100110 |
| _version_ | 1819043978338631680 |
|---|---|
| author | Zhenying Han Sonali Shaligram Marie E. Faughnan Dewi Clark Zhengda Sun Hua Su |
| author_facet | Zhenying Han Sonali Shaligram Marie E. Faughnan Dewi Clark Zhengda Sun Hua Su |
| author_sort | Zhenying Han |
| collection | DOAJ |
| description | Aim: To test if the impairment of mononuclear cell (MNC) migration in patients with hereditary hemorrhagic telangiectasia (HHT) is due to the reduction of the endoglin (ENG) receptor on the cell surface and oxidative stress.
Methods: MNCs of HHT patients and normal controls were subjected to migration assay. Fractions of MNCs were pre-incubated with antibodies specific to HHT causative genes ENG [hereditary hemorrhagic telangiectasia type 1 (HHT1)] or activin receptor-like kinase 1 [ALK1, hereditary hemorrhagic telangiectasia type 2 (HHT2)], AMD3100 or Diprotin-A to block ENG, ALK1 C-X-C chemokine receptor 4 (CXCR4) or CD26 (increased in HHT1 MNCs) before migration assay. The MNCs were allowed to migrate toward stromal cell-derived factor-1α (SDF-1α) for 18 h. The expression of CXCR4, CD26, superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPX1) in MNCs and nitric oxide levels in the plasma were analyzed.
Results: Compared to the controls, fewer HHT1 MNCs and similar number of HHT2 MNCs migrated toward SDF-1α. Diprotin-A pre-treatment improved HHT1 MNC-migration, but had no effect on normal and HHT2 MNCs. Pre-incubation with an anti-ENG antibody reduced the migration of normal MNCs. Diprotin-A did not improve the migration of ENG antibody pre-treated MNCs. Anti-ALK1 antibody had no effect on MNC-migration. AMD3100 treatment reduced normal and HHT MNC-migration. ENG mRNA level was reduced in HHT1 and HHT2 MNCs. ALK1 mRNA was reduced in HHT2 MNCs only. CD26 expression was higher in HHT1 MNCs. Pre-treatment of MNCs with anti-ENG or anti-ALK1 antibody had no effect on CD26 and CXCR4 expression. The expression of antioxidant enzymes, SOD1, was reduced in HHT1 MNCs, which was accompanied with an increase of ROS in HHT MNCs and nitric oxide in HHT1 plasma.
Conclusions: Reduction of ENG receptor on MNC surface reduced monocyte migration toward SDF-1α independent of CD26 expression. Increased oxidative stress could alter HHT MNC migration behavior. |
| first_indexed | 2024-12-21T10:05:22Z |
| format | Article |
| id | doaj.art-e35a65a01ab74c1b85d6c57dc346332d |
| institution | Directory Open Access Journal |
| issn | 2692-3106 |
| language | English |
| last_indexed | 2024-12-21T10:05:22Z |
| publishDate | 2020-06-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Medicine |
| spelling | doaj.art-e35a65a01ab74c1b85d6c57dc346332d2022-12-21T19:07:51ZengOpen Exploration Publishing Inc.Exploration of Medicine2692-31062020-06-011313614810.37349/emed.2020.00010Reduction of endoglin receptor impairs mononuclear cell-migrationZhenying Han0Sonali Shaligram1Marie E. Faughnan2Dewi Clark3Zhengda Sun4Hua Su5Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143, USA; Center for Cerebrovascular Research, University of California, San Francisco, CA 94143, USADepartment of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143, USA; Center for Cerebrovascular Research, University of California, San Francisco, CA 94143, USAToronto HHT Centre, Division of Respirology, Department of Medicine, St. Michael’s Hospital, University of Toronto, Ontario M5B 1W8, Canada; Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto, Ontario M5B 1W8, CanadaToronto HHT Centre, Division of Respirology, Department of Medicine, St. Michael’s Hospital, University of Toronto, Ontario M5B 1W8, CanadaDepartment of Radiology, University of California, San Francisco, CA 94143, USADepartment of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143, USA; Center for Cerebrovascular Research, University of California, San Francisco, CA 94143, USAAim: To test if the impairment of mononuclear cell (MNC) migration in patients with hereditary hemorrhagic telangiectasia (HHT) is due to the reduction of the endoglin (ENG) receptor on the cell surface and oxidative stress. Methods: MNCs of HHT patients and normal controls were subjected to migration assay. Fractions of MNCs were pre-incubated with antibodies specific to HHT causative genes ENG [hereditary hemorrhagic telangiectasia type 1 (HHT1)] or activin receptor-like kinase 1 [ALK1, hereditary hemorrhagic telangiectasia type 2 (HHT2)], AMD3100 or Diprotin-A to block ENG, ALK1 C-X-C chemokine receptor 4 (CXCR4) or CD26 (increased in HHT1 MNCs) before migration assay. The MNCs were allowed to migrate toward stromal cell-derived factor-1α (SDF-1α) for 18 h. The expression of CXCR4, CD26, superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPX1) in MNCs and nitric oxide levels in the plasma were analyzed. Results: Compared to the controls, fewer HHT1 MNCs and similar number of HHT2 MNCs migrated toward SDF-1α. Diprotin-A pre-treatment improved HHT1 MNC-migration, but had no effect on normal and HHT2 MNCs. Pre-incubation with an anti-ENG antibody reduced the migration of normal MNCs. Diprotin-A did not improve the migration of ENG antibody pre-treated MNCs. Anti-ALK1 antibody had no effect on MNC-migration. AMD3100 treatment reduced normal and HHT MNC-migration. ENG mRNA level was reduced in HHT1 and HHT2 MNCs. ALK1 mRNA was reduced in HHT2 MNCs only. CD26 expression was higher in HHT1 MNCs. Pre-treatment of MNCs with anti-ENG or anti-ALK1 antibody had no effect on CD26 and CXCR4 expression. The expression of antioxidant enzymes, SOD1, was reduced in HHT1 MNCs, which was accompanied with an increase of ROS in HHT MNCs and nitric oxide in HHT1 plasma. Conclusions: Reduction of ENG receptor on MNC surface reduced monocyte migration toward SDF-1α independent of CD26 expression. Increased oxidative stress could alter HHT MNC migration behavior.https://www.explorationpub.com/Journals/em/Article/100110endoglinalk1hereditary hemorrhagic telangiectasiamononuclear cellsmigrationoxidative stress |
| spellingShingle | Zhenying Han Sonali Shaligram Marie E. Faughnan Dewi Clark Zhengda Sun Hua Su Reduction of endoglin receptor impairs mononuclear cell-migration Exploration of Medicine endoglin alk1 hereditary hemorrhagic telangiectasia mononuclear cells migration oxidative stress |
| title | Reduction of endoglin receptor impairs mononuclear cell-migration |
| title_full | Reduction of endoglin receptor impairs mononuclear cell-migration |
| title_fullStr | Reduction of endoglin receptor impairs mononuclear cell-migration |
| title_full_unstemmed | Reduction of endoglin receptor impairs mononuclear cell-migration |
| title_short | Reduction of endoglin receptor impairs mononuclear cell-migration |
| title_sort | reduction of endoglin receptor impairs mononuclear cell migration |
| topic | endoglin alk1 hereditary hemorrhagic telangiectasia mononuclear cells migration oxidative stress |
| url | https://www.explorationpub.com/Journals/em/Article/100110 |
| work_keys_str_mv | AT zhenyinghan reductionofendoglinreceptorimpairsmononuclearcellmigration AT sonalishaligram reductionofendoglinreceptorimpairsmononuclearcellmigration AT marieefaughnan reductionofendoglinreceptorimpairsmononuclearcellmigration AT dewiclark reductionofendoglinreceptorimpairsmononuclearcellmigration AT zhengdasun reductionofendoglinreceptorimpairsmononuclearcellmigration AT huasu reductionofendoglinreceptorimpairsmononuclearcellmigration |