Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3

Stein, Torsten; Morris, Joanna S.; Davies, Claire; Weber-Hall, Stephen J.; Duffy, Marie-Anne; Heath, Victoria J.; Bell, Alison M.; Ferrier, Roderick K.; Sandilands, G. P.; Gusterson, Barry A.

doi:10.1186/bcr753

Cited by 325 publications

(212 citation statements)

References 61 publications

(46 reference statements)

Supporting

Mentioning

194

Contrasting

Unclassified

Order By: Relevance

“…In this process, the remaining MFGs are also cleared from the gland (8). The involution process is regulated at the transcriptional level and is associated with the up-or down-regulation of a set of genes (26,27). In this report, we showed that the MFG-E8 gene was strongly expressed in the mammary gland during the lactation and involution periods.…”

Section: Discussionmentioning

confidence: 57%

“…However, our mice were maintained in specific pathogen-free conditions, and mastitis was never found in the WT mice, suggesting that the mastitis in the MFG-E8 Ϫ/Ϫ mice was induced without bacterial infection. The involution of the mammary gland is regulated by the STAT3 transcription factor (31,32) and is accompanied by the activation of various inflammatory genes such as CXCL1 and CXCL10 (27), which recruit inflammatory cells into the mammary gland. It is possible that the prolonged involution process in MFG-E8 Ϫ/Ϫ mice causes the extended activation of inflammatory genes, leading to severe inflammation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8

Hanayama

Nagata

2005

Proc. Natl. Acad. Sci. U.S.A.

120

118

View full text Add to dashboard Cite

During the involution of mammary glands, epithelial cells undergo apoptosis and are cleared for the next cycle of lactation. The clearance of apoptotic epithelial cells is mediated by neighboring epithelial cells and by macrophages that migrate into the mammary glands. Here, we report that milk fat globule EGF factor 8 (MFG-E8), a secreted glycoprotein that binds to apoptotic cells by recognizing phosphatidylserine, was expressed by epithelial cells and macrophages in mammary glands and was involved in engulfment of apoptotic cells. A deficiency of MFG-E8 caused the accumulation of a large number of milk fat globules (MFGs) in the mammary ducts during involution, indicating that the excess MFGs were cleared by an MFG-E8-dependent mechanism. The MFG-E8 ؊/؊ mice developed mammary duct ectasia with periductal mastitis, and the redevelopment of the mammary gland for their second litter was impaired. These results demonstrate that MFG-E8-mediated phagocytosis of apoptotic epithelial cells and MFGs is important for efficient involution of mammary glands.exosomes ͉ mastitis ͉ phosphatidylserine M ammary glands are unique mammalian organs that are developed to nurse offspring. For each pregnancy, the glands undergo a cycle of development, lactation, and involution. In each cycle, mammalian epithelial cells proliferate, differentiate, and die. The involution of mammary glands is triggered when the suckling stimulus is lost, usually upon weaning, and milk accumulates in the glands. The involution takes Ϸ10 days in mice and can be divided into two phases (1-3). In the first phase, which is reversible and lasts 48 h after weaning, mammary epithelial cells lose their differentiated function. In the second phase, the basement membranes and extracellular matrix in the mammary glands are degraded by proteases, leading to destruction of the lobular-alveolar architecture of the mammary glands. As involution progresses, mammary epithelial cells are removed and adipocytes concomitantly reappear, and the lobular-alveolar structure is reorganized to approach that of virgin glands (4).During the involution process, epithelial cells undergo apoptosis and are shed into the lumen (5). At the initial stage of involution, these apoptotic cells are thought to be engulfed mainly by neighboring epithelial cells; in the later stage, they seem to be cleared by macrophages that migrate into the gland (3, 6). Milk fat globules (MFGs) are minute globules carrying fat that are secreted from the epithelial cells into the lumen during lactation (7). Upon weaning, many MFGs remain in the lumen, and they seem to be engulfed by epithelial cells lining the lobules in the mammary gland (8). How these epithelial cells and macrophages recognize and engulf apoptotic cells and MFGs has not been well elucidated.Many molecules expressed on the surface of apoptotic cells or phagocytes have been proposed as ligands and receptors for the engulfment of apoptotic cells (9 -11). Mouse MFG EGF factor 8 (MFG-E8), called lactadherin in humans, is a 72-kDa glycoprotein s...

show abstract

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8

Hanayama

Nagata

2005

Proc. Natl. Acad. Sci. U.S.A.

120

118

View full text Add to dashboard Cite

show abstract

“…Using microarray analysis, Stein et al identified a set of genes specifically upregulated during the initial 4 days of involution (54). Further analysis of gene function revealed a set of genes associated with a wound-healing response, specifically neutrophil and macrophage activation.…”

Section: Involutionmentioning

confidence: 99%

Immune Cell Location and Function During Post-Natal Mammary Gland Development

Reed

Schwertfeger

2010

J Mammary Gland Biol Neoplasia

View full text Add to dashboard Cite

Post-natal mammary gland development requires complex interactions between the epithelial cells and various cell types within the stroma. Recent studies have illustrated the importance of immune cells and their mediators during the various stages of mammary gland development. However, the mechanisms by which these immune cells functionally contribute to mammary gland development are only beginning to be understood. This review provides an overview of the localization of immune cells within the mammary gland during the various stages of post-natal mammary gland development. Furthermore, recent studies are summarized that illustrate the mechanisms by which these cells are recruited to the mammary gland and their functional roles in mammary gland development.

show abstract

“…Following pregnancy and lactation, the alveolar mammary epithelium (which produces milk during lactation) undergoes widespread synchronized apoptosis, removing up to 90% of the mammary epithelium within only 7–10 days. This involution process returns the mammary epithelium to a quiescent state capable of future rounds of alveolar budding and pregnancy-induced expansion [3, 4] . While the mammary gland represents a rather dramatic example of physiological cell death, most tissues harbor some level of cell death at any given time.…”

Section: Introductionmentioning

confidence: 99%

“…Regulation of cytokine and chemokine production is mediated by macrophages, with these cytokines and chemokines instructing the response of the cells in the adaptive immune system. Efferocytosis is critical to macrophage-mediated suppression of adaptive immune responses and resolution of inflammation [4, 6] . Efferocytosis resembles other categories of phagocytosis in many ways.…”

Section: Introductionmentioning

confidence: 99%

Efferocytosis Creates a Tumor Microenvironment Supportive of Tumor Survival and Metastasis

Vaught

Stanford

Cook

2015

Can Cell Microenviron

View full text Add to dashboard Cite

Programmed cell death, or apoptosis, occurs in nearly all tissues of all multi-cellular organisms. In order to avoid leakage of intracellular contents, which could generate tissue damaging inflammation, apoptotic cells are cleared from tissues by phagocytes, which then dispatch the engulfed dying cell through the lysosomal pathway. Phagocytic clearance of apoptotic cells is referred to as efferocytosis. One key feature of efferocytosis is the production and release of wound healing cytokines by the phagocyte, which acts to resolve inflammation, and promote tissue repair. Phagocytic engulfment of apoptotic cells coupled with cytokine modulation aimed at immune suppression ensures that physiological programmed cell death does not induce inflammation and tissue damage. However, cytokines involved in wound healing and immune suppression are notorious for their role in the tumor microenvironment, increasing tumor cell motility and promoting evasion of anti-tumor immunity. Therefore, current and future studies aimed at targeting important players of efferocytosis should reveal new and efficacious therapeutic approaches for limiting cancer progression and relapse.

show abstract

Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3

Cited by 325 publications

References 61 publications

Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8

Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8

Immune Cell Location and Function During Post-Natal Mammary Gland Development

Efferocytosis Creates a Tumor Microenvironment Supportive of Tumor Survival and Metastasis

Contact Info

Product

Resources

About