Reciprocal Interaction between Pericytes and Macrophage in Poststroke Tissue Repair and Functional Recovery

Tomoya Shibahara, Tetsuro Ago, Masaki Tachibana, Kuniyuki Nakamura, Kei Yamanaka, Junya Kuroda, Yoshinobu Wakisaka, Takanari Kitazono

研究成果: Contribution to journalArticle査読

5 被引用数 (Scopus)

抄録

Background and Purpose: Poststroke tissue repair, comprised of macrophage-mediated clearance of myelin debris and pericyte-mediated fibrotic response within the infarct area, is an important process for functional recovery. Herein, we investigated the reciprocal interaction between pericytes and macrophages during poststroke repair and functional recovery. Methods: We performed a permanent middle cerebral artery occlusion in both wild-type and pericyte-deficient PDGFRβ (platelet-derived growth factor receptor β) heterozygous knockout (Pdgfrb+/-) mice and compared histological changes and neurological functions between the 2 groups. We also examined the effects of conditioned medium harvested from cultured pericytes, or bone marrow-derived macrophages, on the functions of other cell types. Results: Localization of PDGFRβ-positive pericytes and F4/80-positive macrophages was temporally and spatially very similar following permanent middle cerebral artery occlusion. Intrainfarct accumulation of macrophages was significantly attenuated in Pdgfrb+/-mice. Intrainfarct pericytes expressed CCL2 (C-C motif ligand 2) and CSF1 (colony stimulating factor 1), both of which were significantly lower in Pdgfrb+/-mice. Cultured pericytes expressed Ccl2 and Csf1, both of which were significantly increased by PDGF-BB and suppressed by a PDGFRβ inhibitor. Pericyte conditioned medium significantly enhanced migration and proliferation of bone marrow-derived macrophages. Poststroke clearance of myelin debris was significantly attenuated in Pdgfrb+/-mice. Pericyte conditioned medium promoted phagocytic activity in bone marrow-derived macrophages, also enhancing both STAT3 (signal transducer and activator of transcription 3) phosphorylation and expression of scavenger receptors, Msr1 and Lrp1. Macrophages processing myelin debris produced trophic factors, enhancing PDGFRβ signaling in pericytes leading to the production of ECM (extracellular matrix) proteins and oligodendrogenesis. Functional recovery was significantly attenuated in Pdgfrb+/-mice, parallel with the extent of tissue repair. Conclusions: A reciprocal interaction between pericytes and macrophages is important for poststroke tissue repair and functional recovery.

本文言語英語
ページ(範囲)3095-3106
ページ数12
ジャーナルStroke
DOI
出版ステータス出版済み - 10 1 2020

All Science Journal Classification (ASJC) codes

  • 臨床神経学
  • 循環器および心血管医学
  • 高度および特殊看護

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