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Updated: Sep 14, 2025
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Immunoreceptor CD300a regulates ischemic tissue damage and adverse remodeling in the mouse heart and kidney
Nanako Nishiyama1,2, Hitoshi Koizumi1,2,3, Chigusa Nakahashi-Oda1,4
1Department of Immunology, Institute of Medicine.
Insights
Mice lacking CD300a showed reduced tissue damage after ischemia and reperfusion. This was due to improved efferocytosis and decreased harmful neutrophils, leading to milder heart and kidney disease progression.
Area of Science:
- Immunology
- Pathology
- Cardiology
- Nephrology
Background:
- Acute ischemic organ diseases, like myocardial infarction and kidney injury, can lead to chronic heart failure and kidney disease.
- The precise molecular mechanisms driving these chronic conditions are not fully understood.
Purpose of the Study:
- To investigate the role of CD300a, an inhibitory immunoreceptor, in the pathogenesis of ischemic tissue injury and adverse remodeling.
- To explore the impact of CD300a deficiency on immune responses and tissue repair following ischemia-reperfusion injury.
Main Methods:
- Utilized a mouse model deficient in CD300a.
- Analyzed efferocytosis by tissue-resident macrophages and neutrophil populations (SiglecFhi and SiglecFlo) after ischemia-reperfusion (IR) injury.
- Assessed tissue damage, inflammation, and adverse remodeling in the heart and kidney.
Main Results:
- CD300a-deficient mice exhibited enhanced efferocytosis and reduced pathogenic neutrophils, leading to less inflammation-associated tissue injury post-IR.
- Absence of CD300a on SiglecFlo neutrophils promoted signal transducer and activator of transcription 3 (STAT3)-mediated production of pro-angiogenic and anti-fibrotic factors.
- This resulted in significantly milder adverse remodeling in the heart and kidney compared to wild-type mice.
Conclusions:
- CD300a plays a critical role in mediating tissue damage and adverse remodeling following ischemic injury.
- Targeting CD300a may offer a therapeutic strategy to mitigate chronic heart failure and chronic kidney disease progression after acute ischemic events.
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.
