title: Human albumin attenuates excessive innate immunity via inhibition of microglial Mincle/Syk signaling in subarachnoid hemorrhage.
abstract: Subarachnoid hemorrhage (SAH) is a devastating subtype of stroke. Microglial macrophage-inducible C-type lectin (Mincle) receptor launches microglial innate immunity after SAH, and thereby achieves a key step of early cerebral injury in SAH. We previously revealed albumin could improve long-term neurological outcomes after SAH. In this study, we examined the role of microglia-mediated innate immunity in the salutary effects of albumin. SAH was induced by endovascular perforation in rats. We found that albumin can significantly mitigate early neurovascular dysfunction of SAH rats. Albumin administration resulted in reduced Iba-1 and CD68 staining in cortex. Markers of microglia M1 polarization (iNOS, IL-1β, CD16, and CD32) were remarkably suppressed. Neutrophil invasion was inhibited as chemokines (MCP-1, CINC-1, and CXCL-2) mRNA levels, myeloperoxidase (MPO) and intracellular adhesion molecule-1 (ICAM-1) expressions were decreased. Mechanistically, albumin bound with microglial Mincle receptor, and retarded Mincle/Syk/IL-1β signaling in ipsilateral hemisphere subjected to SAH. In the cultured BV-2 microglial cells, we found Mincle and its ligand SAP130 mediate the cross-talk between neuronal necroptosis and microglial immunity response following SAH-related injury. Albumin could attenuate SAP130-induced Mincle upregulation and subsequent microglial inflammatory responses. The anti-inflammation effect of albumin was similar to the effect of genetic knockdown of Mincle. This effect may be attributed to a direct association between albumin and Mincle. The interaction also yielded a depression in the initiation of Mincle/Syk/IL-1β pathway. In conclusion, our results indicate that albumin can ameliorate innate immune responses after SAH. This anti-inflammatory action may be through direct restraining microglial Mincle receptor.
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210000, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210000, China.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210000, China.
authors.forename: Liumin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210000, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, China.
authors.forename: Xiaohao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210000, China.
authors.forename: Linjie
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210000, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210000, China.
authors.forename: Yunzi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210000, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210000, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210000, China. Electronic address: yeruid@gmail.com.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Ye
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210000, China. Electronic address: xfliu2@vip.163.com.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000188:drug therapy; D007113:Immunity, Innate / Q000187:drug effects*; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000075462:Serum Albumin, Human / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy*; D000072377:Syk Kinase / Q000187:drug effects
chemical_list: D000072377:Syk Kinase; D000075462:Serum Albumin, Human
keywords: Albumin; Microglia; Mincle; Subarachnoid hemorrhage