Epithelial cell-directed efferocytosis in the post-partum mammary gland is necessary for tissue homeostasis and future lactation
| Autor: | Melissa Sandahl, Debra Hunter, Karen E. Strunk, H. Shelton Earp, Rebecca S. Cook |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Mammary gland Apoptosis Mice Transgenic C-Mer Tyrosine Kinase Biology Polymerase Chain Reaction 03 medical and health sciences Mice 0302 clinical medicine Mammary Glands Animal Phagocytosis Internal medicine Proto-Oncogene Proteins medicine Animals Homeostasis Lactation Involution (medicine) Efferocytosis lcsh:QH301-705.5 Tissue homeostasis 030304 developmental biology 0303 health sciences c-Mer Tyrosine Kinase Macrophages Receptor Protein-Tyrosine Kinases Epithelial Cells MERTK Axl Receptor Tyrosine Kinase Epithelium Mice Inbred C57BL medicine.anatomical_structure Endocrinology lcsh:Biology (General) Mammary Epithelium 030220 oncology & carcinogenesis Cancer research Female Developmental Biology Research Article |
| Zdroj: | BMC Developmental Biology BMC Developmental Biology, Vol 10, Iss 1, p 122 (2010) |
| ISSN: | 1471-213X |
| Popis: | Background Mammary glands harbor a profound burden of apoptotic cells (ACs) during post-lactational involution, but little is known regarding mechanisms by which ACs are cleared from the mammary gland, or consequences if this process is interrupted. We investigated AC clearance, also termed efferocytosis, during post-lactational remodeling, using mice deficient for MerTK, Axl, and Tyro3, three related receptor tyrosine kinases (RTKs) regulating macrophage-mediated efferocytosis in monocytes. MerTK expression, apoptosis and the accumulation of apoptotic debris were examined in histological sections of MerTK-deficient, Axl/Tyro3-deficient, and wild-type mammary glands harvested at specific time points during lactation and synchronized involution. The ability of primary mammary epithelial cells (MECs) to engulf ACs was assessed in culture. Transplant of MerTK-deficient mammary epithelium into cleared WT mammary fat pads was used to assess the contribution of WT mammary macrophages to post-lactational efferocytosis. Results ACs induced MerTK expression in MECs, resulting in elevated MerTK levels at the earliest stages of involution. Loss of MerTK resulted in AC accumulation in post-lactational MerTK-deficient mammary glands, but not in Axl and Tyro3-deficient mammary glands. Increased vascularization, fibrosis, and epithelial hyperproliferation were observed in MerTK-deficient mammary glands through at least 60 days post-weaning, due to failed efferocytosis after lactation, but did not manifest in nulliparous mice. WT host-derived macrophages failed to rescue efferocytosis in transplanted MerTK-deficient mammary epithelium. Conclusion Efferocytosis by MECs through MerTK is crucial for mammary gland homeostasis and function during the post-lactational period. Efferocytosis by MECs thus limits pathologic consequences associated with the apoptotic load following lactation. |
| Databáze: | OpenAIRE |
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