A study on efferocytosis in the heart

Abstract

Billions of cells in our body everyday undergo apoptosis but these cells are rarely observed due to their prompt and efficient removal, called efferocytosis. Efferocytosis occurs whenever and wherever an apoptotic cell is generated and contributes to tissue homeostasis and immune regulation. The consequences of efferocytosis in several organs has been investigated. However, if and how engulfment of apoptotic cells in the heart occurs remains elusive. Here, we report that efferocytosis by cardiac fibroblast in the heart is phenomenal, and Axl plays essential roles in efferocytosis in the heart. Efferocytosis by cardiac fibroblast was substantial whereas that by cardiomyocytes was negligible. The removal of apototic cells by cardiac fibroblasts was inhibted by Cyto D, ML-4 and NaN3. Based on qRTPCR and flow cytometry, we found that Axl among TAM family receptors was predominately expressed in cardiac fibroblast. Efferocytosis by cardiac fibroblast was inhibited by Axl specific or pan-TAM receptors inhibitors. Moreover, cardiac fibroblasts derived from Axl depleted mice showed a lower percentage of cardiac fibroblast engulfing apoptotic cells than wild-type cardiac fibroblasts. Taken together, this study suggests that the heart is one of organs where efferocytosis occurs, and Axl predominately expressed in cardiac fibroblasts plays an essential role in efferocytosis in the heart.