title: Macrophages Mediate the Repair of Brain Vascular Rupture through Direct Physical Adhesion and Mechanical Traction.
abstract: Hemorrhagic stroke and brain microbleeds are caused by cerebrovascular ruptures. Fast repair of such ruptures is the most promising therapeutic approach. Due to a lack of high-resolution in vivo real-time studies, the dynamic cellular events involved in cerebrovascular repair remain unknown. Here, we have developed a cerebrovascular rupture system in zebrafish by using multi-photon laser, which generates a lesion with two endothelial ends. In vivo time-lapse imaging showed that a macrophage arrived at the lesion and extended filopodia or lamellipodia to physically adhere to both endothelial ends. This macrophage generated mechanical traction forces to pull the endothelial ends and facilitate their ligation, thus mediating the repair of the rupture. Both depolymerization of microfilaments and inhibition of phosphatidylinositide 3-kinase or Rac1 activity disrupted macrophage-endothelial adhesion and impaired cerebrovascular repair. Our study reveals a hitherto unexpected role for macrophages in mediating repair of cerebrovascular ruptures through direct physical adhesion and mechanical traction.
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Wu
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China.
authors.forename: Qifen
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Endodontics and Operative Dentistry, Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, The Affiliated Hospital of Stomatology, Chongqing Medical University, 401147 Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Endodontics and Operative Dentistry, Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, The Affiliated Hospital of Stomatology, Chongqing Medical University, 401147 Chongqing, China. Electronic address: yangdeqin@gmail.com.
authors.forename: Deqin
authors.initials: D
authors.lastname: Yang
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China. Electronic address: lluo@swu.edu.cn.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Luo
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D017542:Aneurysm, Ruptured / Q000276:immunology*; D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D020214:Cerebrovascular Trauma / Q000276:immunology*; D004730:Endothelium, Vascular / Q000502:physiology*; D008264:Macrophages / Q000276:immunology*; D055595:Mechanical Phenomena; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014143:Traction; D066253:Vascular Remodeling; D014945:Wound Healing; D015027:Zebrafish / Q000276:immunology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D020830:rac1 GTP-Binding Protein