PMID- 22129827
OWN - NLM
STAT- MEDLINE
DCOM- 20120208
LR  - 20111221
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Linking)
VI  - 139
IP  - 2
DP  - 2012 Jan
TI  - Macrophages are crucial for epithelial cell death and adipocyte repopulation 
      during mammary gland involution.
PG  - 269-75
LID - 10.1242/dev.071696 [doi]
AB  - Mammary gland development is dependent on macrophages, as demonstrated by their 
      requirement during the expansion phases of puberty and pregnancy. Equally 
      dramatic tissue restructuring occurs following lactation, when the gland 
      regresses to a state that histologically resembles pre-pregnancy through massive 
      programmed epithelial cell death and stromal repopulation. Postpartum involution 
      is characterized by wound healing-like events, including an influx of macrophages 
      with M2 characteristics. Macrophage levels peak after the initial wave of 
      epithelial cell death, suggesting that initiation and execution of cell death are 
      macrophage independent. To address the role of macrophages during weaning-induced 
      mammary gland involution, conditional systemic deletion of macrophages expressing 
      colony stimulating factor 1 receptor (CSF1R) was initiated just prior to weaning 
      in the Mafia mouse model. Depletion of CSF1R(+) macrophages resulted in delayed 
      mammary involution as evidenced by loss of lysosomal-mediated and apoptotic 
      epithelial cell death, lack of alveolar regression and absence of adipocyte 
      repopulation 7 days post-weaning. Failure to execute involution occurred in the 
      presence of milk stasis and STAT3 activation, indicating that neither is 
      sufficient to initiate involution in the absence of CSF1R(+) macrophages. 
      Injection of wild-type bone marrow-derived macrophages (BMDMs) or 
      M2-differentiated macrophages into macrophage-depleted mammary glands was 
      sufficient to rescue involution, including apoptosis, alveolar regression and 
      adipocyte repopulation. BMDMs exposed to the postpartum mammary involution 
      environment upregulated the M2 markers arginase 1 and mannose receptor. These 
      data demonstrate the necessity of macrophages, and implicate M2-polarized 
      macrophages, for epithelial cell death during normal postpartum mammary gland 
      involution.
FAU - O'Brien, Jenean
AU  - O'Brien J
AD  - School of Medicine, Division of Medical Oncology, University of Colorado Anschutz 
      Medical Campus, Aurora, CO 80045, USA.
FAU - Martinson, Holly
AU  - Martinson H
FAU - Durand-Rougely, Clarissa
AU  - Durand-Rougely C
FAU - Schedin, Pepper
AU  - Schedin P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20111130
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Adipocytes/*physiology
MH  - Animals
MH  - Blotting, Western
MH  - Cell Death/*physiology
MH  - Epithelial Cells/*physiology
MH  - Female
MH  - Flow Cytometry
MH  - Immunohistochemistry
MH  - Macrophages/metabolism/*physiology
MH  - Mammary Glands, Animal/*cytology/*physiology
MH  - Mice
MH  - Postpartum Period/*physiology
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptor, Macrophage Colony-Stimulating Factor/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Weaning
EDAT- 2011/12/02 06:00
MHDA- 2012/02/09 06:00
CRDT- 2011/12/02 06:00
PHST- 2011/12/02 06:00 [entrez]
PHST- 2011/12/02 06:00 [pubmed]
PHST- 2012/02/09 06:00 [medline]
AID - dev.071696 [pii]
AID - 10.1242/dev.071696 [doi]
PST - ppublish
SO  - Development. 2012 Jan;139(2):269-75. doi: 10.1242/dev.071696. Epub 2011 Nov 30.