Macrophages and Apoptotic Cell Clearance During Pregnancy

Abrahams, Vikki M.; Kim, Yeon Mee; Straszewski, Shawn; Romero, Roberto; Mor, Gil

doi:10.1111/j.1600-0897.2004.00156.x

Cited by 310 publications

(239 citation statements)

References 55 publications

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“…The decidua comprises several cell types, but our present study shows that DMs are the major decidual cell type producing TNF-a in response to LPS challenge. The roles of DMs in the maintenance of early pregnancy have been examined in terms of antigen presentation, immunoregulation, and lymphokine production (Abrahams et al 2004). The DMs present in human early decidual tissue have a capacity for allo-antigen presentation, a higher suppressive activity, and a lower capacity to produce IL-1 following LPS stimulation than peripheral blood monocytes (Mizuno et al 1994).…”

Section: Discussionmentioning

confidence: 99%

“…DMs may also produce cytokines such as IL-1, TNF-a and IL-6 in response to an infection and therefore cause an intrauterine inflammatory reaction that could provoke preterm parturition (McGregor et al 1988). Moreover, during implantation DMs have an important role in the regulation of apoptosis which is critical for the invasion of the developing embryo (Abrahams et al 2004) and have several biochemical functions that favour local immunological tolerance against fetal tissues (Heikkinen et al 2003).…”

Section: Introductionmentioning

confidence: 99%

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Immunological properties of human decidual macrophages – a possible role in intrauterine immunity

Singh¹,

Nicholson²,

Urban³

et al. 2005

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Our aim was to investigate the contribution of decidual macrophages, which constitute an important immune component of the decidua in late gestation, to intrauterine defence mechanisms. Using flow cytometry we examined the ability of decidual macrophages, isolated from term decidua, to bind and phagocytose fluorescence-labelled bacterial and yeast bioparticles. We also assessed their ability to generate superoxide radicals and tumour necrosis factor-a following lipopolysaccharide challenge. Decidual macrophages bound bacterial and yeast particles in a dose-dependent manner, which subsequently led to phagocytosis. These macrophages also produced superoxide radicals and the pro-inflammatory cytokine TNF-a when challenged with bacterial lipopolysaccharides. These results suggest a role for decidual macrophages in pathogen recognition and clearance during pregnancy, and, therefore, they are likely to protect the fetus against intrauterine infections which might otherwise lead to preterm labour.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunological properties of human decidual macrophages – a possible role in intrauterine immunity

Singh¹,

Nicholson²,

Urban³

et al. 2005

Reproduction

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“…Based on their lysosomal enzyme content (Bulmer and Johnson, 1984) and proximity to apoptotic cells in situ it has been proposed that they play a role in phagocytosis of cell debris produced during implantation (reviewed in Mor and Abrahams, 2003;Abrahams et al, 2004). A role in immunosuppression has also been proposed due to their suppression of one-way mixed lymphocyte reaction (Mizuno et al, 1994).…”

Section: Functional Studiesmentioning

confidence: 99%

Immune cells in the placental bed

Bulmer¹,

Williams²,

Lash³

2010

Int. J. Dev. Biol.

319

280

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“…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).…”

mentioning

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

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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...

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Macrophages and Apoptotic Cell Clearance During Pregnancy

Abstract: The function of the maternal immune system during implantation and throughout pregnancy is, therefore, an important area of investigation. This review will discuss the role of decidual macrophages in apoptotic cell clearance during pregnancy.

Cited by 310 publications

References 55 publications

Immunological properties of human decidual macrophages – a possible role in intrauterine immunity

Immunological properties of human decidual macrophages – a possible role in intrauterine immunity

Immune cells in the placental bed

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

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