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Epithelial Cells Remove Apoptotic Epithelial Cells During Post-Lactation Involution of the Mouse Mammary Gland¹

Program in Cell Biology, Department of Pediatrics, National Jewish Medical & Research Center, Denver, Colorado 80206

ABSTRACT

Following the cessation of lactation, the mammary gland undergoes a physiologic process of tissue remodeling called involution in which glandular structures are lost, leaving an adipose tissue compartment that takes up a much larger proportion of the tissue. A quantitative morphometric analysis was undertaken to determine the mechanisms for clearance of the epithelial cells during this process. The involution process was set in motion by removal of pups from 14-day lactating C57BL/6 mice. Within hours, milk-secreting epithelial cells were shed into the glandular lumen. These cells became apoptotic, exhibiting exposure of phosphatidylserine residues on their surfaces, activation of effector caspase-3, staining for caspase-cleaved keratin 18, loss of internal organellar structure, and nuclear breakdown, but minimal blebbing or generation of apoptotic bodies. Clearance of residual milk and the shed epithelial cells was rapid, with most of the removal occurring in the first 72 h. Intact apoptotic epithelial cells were engulfed in large numbers by residual viable epithelial cells into spacious efferosomes. This process led to essentially complete involution within 4 days, at which point estrous cycling recommenced. Macrophages and other inflammatory cells did not contribute to the clearance of either residual milk or apoptotic cells, which appeared to be due entirely to the epithelium itself.

apoptosis, efferocytosis, immunology, involution, mammary glands, mammary involution, phagocytosis

¹Supported by NIH grants PO1 HD 38129 and RO1 GM 061031.

Correspondence: ²Jenifer Monks, Reproductive Sciences, Ob/Gyn, MS 8309, University of Colorado Health Sciences Center, Anschutz Medical Campus, P.O. Box 6511, 12800 E. 19th Ave., Aurora, CO 80045. FAX: 303 724 3512; e-mail: Jenifer.Monks{at}UCHSC.edu