Immunoreceptor CD300a regulates ischemic tissue damage and adverse remodeling in the mouse heart and kidney
Nanako Nishiyama, Hitoshi Koizumi, Chigusa Nakahashi-Oda, Satoshi Fujiyama, Xuewei Ng, Hanbin Lee, Fumie Abe, Jinao Li, Yan Xu, Takehito Sugasawa, Kazuko Tajiri, Taketaro Sadahiro, Masaki Ieda, Keiji Tabuchi, Kazuko Shibuya, Akira Shibuya
Nanako Nishiyama, Hitoshi Koizumi, Chigusa Nakahashi-Oda, Satoshi Fujiyama, Xuewei Ng, Hanbin Lee, Fumie Abe, Jinao Li, Yan Xu, Takehito Sugasawa, Kazuko Tajiri, Taketaro Sadahiro, Masaki Ieda, Keiji Tabuchi, Kazuko Shibuya, Akira Shibuya
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Research Article Immunology Inflammation

Immunoreceptor CD300a regulates ischemic tissue damage and adverse remodeling in the mouse heart and kidney

Abstract

Acute ischemic organ diseases such as acute myocardial infarction and acute kidney injury often result in irreversible tissue damage and progress to chronic heart failure (CHF) and chronic kidney disease (CKD), respectively. However, the molecular mechanisms underlying the development of CHF and CKD remain incompletely understood. Here, we show that mice deficient in CD300a, an inhibitory immunoreceptor expressed on myeloid cells, showed enhanced efferocytosis by tissue-resident macrophages and decreased damage-associated molecular patterns and pathogenic SiglecFhi neutrophils, resulting in milder inflammation-associated tissue injury than in wild-type mice after ischemia and reperfusion (IR). Notably, we uncovered that CD300a deficiency on SiglecFlo neutrophils increased the signal transducer and activator of transcription 3–mediated production of pro-angiogenic and antifibrotic factors, resulting in milder adverse remodeling after IR. Our results demonstrated that CD300a plays an important role in the pathogenesis of ischemic tissue injury and adverse remodeling in the heart and kidney.

Authors

Nanako Nishiyama, Hitoshi Koizumi, Chigusa Nakahashi-Oda, Satoshi Fujiyama, Xuewei Ng, Hanbin Lee, Fumie Abe, Jinao Li, Yan Xu, Takehito Sugasawa, Kazuko Tajiri, Taketaro Sadahiro, Masaki Ieda, Keiji Tabuchi, Kazuko Shibuya, Akira Shibuya

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Figure 6

Anti-CD300a mAb ameliorates tissue injury and adverse remodeling.

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Anti-CD300a mAb ameliorates tissue injury and adverse remodeling. (A) Pl...
(A) Plasma cTnI in anti-CD300a mAb– or Ctrl-administered mice (n = 7 or 8). (B) CD31+ capillary density in peri-infarct area in anti-CD300a mAb– or Ctrl-administered mice (n = 7). (C) LVFS and LVEF in anti-CD300a mAb– or Ctrl-administered mice (n = 7 or 5). (D) Masson’s trichrome staining and the fibrosis area in the ventricle in anti-CD300a mAb– or Ctrl-administered mice (n = 10 or 11). (E) Efferocytosis of GFP+ dead cells by myeloid cell subpopulations in the cardiac tissue of αMHC-GFP mice given anti-CD300a mAb or Ctrl (n = 6 or 7). (F) Generation of BM chimeric R26GRR mice (GFP+ mice) and efferocytosis of host-derived GFP+ dead cells by resident macrophages of the chimeric mice given an anti-CD300a mAb (n = 8 or 5) or Ctrl (n = 5 or 4). (G) Plasma BUN and Cre in WT and Cd300b–/– mice given anti-CD300a mAb or Ctrl (WT, n = 3 or 17; Cd300b–/–, n = 5 or 6). (H) Periodic acid–Schiff staining of the kidney and acute tubular necrosis (ATN) score in mice given anti-CD300a mAb or Ctrl (n = 9 in each group). (I) Sirius red staining and the fibrosis area in WT and Cd300b–/– mice given anti-CD300a mAb or Ctrl (WT, n = 8; Cd300b–/–, n = 5 or 6). Scale bars: 100 μm (B, H, and I) and 1 mm (D). Data are presented as mean ± SEM and pooled from 2 (A–D, F, H, and I) and 5 (E and G) experiments. Student’s t test (A–D and H) and 2-way ANOVA (E–G and I). *P < 0.05; **P < 0.01; ***P < 0.001.