Evidence of specialized leukocyte-vascular homing interactions at the maternal / fetal interface

Kruse, Andrea; Merchant, Milton; Hallmann, Rupert; Butcher, Eugene C.

doi:10.1002/(sici)1521-4141(199904)29:04<1116::aid-immu1116>3.0.co;2-4

Cited by 65 publications

(44 citation statements)

References 31 publications

(26 reference statements)

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“…The expression of homing-associated molecules at the maternal/fetal interface of normal pregnancies was described recently [9,10]. This study will focus on the unusual co-expression of MAdCAM-1 and P-selectin observed on maternal vessels of the vascular zone at day 9 of gestation and on the functional involvement of these vascular addressins in leukocyte traffic to the decidua basalis.…”

Section: Resultsmentioning

confidence: 97%

“…Maternal vessels in each of these microenvironments display unique patterns of adhesion molecules and appear to support vascular interactions with distinct subsets of circulating leukocytes [9]. One of the most striking features is the unusual co-expression of MAdCAM-1 and P-selectin on vessels of the vascular zone.…”

Section: Discussionmentioning

confidence: 99%

“…It is appropriate to emphasize that the decidua represents a highly complex tissue in which leukocyte trafficking needs to be exquisitely regulated to allow entry of specialized subsets hypothesized to support and reg- [DOI 10.1002/eji.200425223] ulate trophoblast invasion and local immune responses. The highly regulated expression of vascular addressins in the decidua may be fundamental to this process [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

et al. 2004

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Leukocyte recruitment to the pregnant mouse uterus has been suggested to be associated with highly regulated expression of distinct patterns of vascular adhesion receptors. One of the most striking observations is the combined expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and P-selectin by maternal vessels of the vascular zone during the critical period of initial placenta development. The predominant cell population within these vessels is of the monocyte/macrophage lineage and expresses the mucosal integrin a4b7, which represents the ligand for MAdCAM-1; neutrophils and lymphocytes are rare. To directly assess the importance of identified adhesion receptors, we undertook longterm in vivo inhibition studies using monoclonal antibodies to inhibit the contribution of MAdCAM-1 in leukocyte trafficking to the decidua or to deplete a4b7 + leukocytes. In addition, implantation sites of mouse strains genetically deficient in specific adhesion receptors were investigated. Our results underline the importance of predicted adhesion pathways in the recruitment of monocyte-like cells, especially those expressing a4b7. Interestingly, maternal/ fetal units with inhibited recruitment of a4b7 + leukocytes or the absence of these cells are characterized by reduced size and frequency of uterine NK cells.

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

et al. 2004

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“…MAdCAM-1 was expressed in an aberrant location, and VCAM-1 expression was less intense. VCAM-1 is thought to be the key addressin in early uNK cell recruitment to deciduas basalis (48). The successful localization of many uNK cells in diabetic NOD pregnancy supports this postulate (48).…”

Section: Discussionmentioning

confidence: 95%

“…VCAM-1 is thought to be the key addressin in early uNK cell recruitment to deciduas basalis (48). The successful localization of many uNK cells in diabetic NOD pregnancy supports this postulate (48). Homing receptor elevation underlies insulitis, which is present in all adult NOD mice, regardless of diabetic state.…”

Section: Discussionmentioning

confidence: 95%

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

et al. 2007

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OBJECTIVE-Pregnant diabetic women are at a 4 -12 times higher risk for preeclampsia, an urgent acute-onset complication of mid-to late gestation, than normal pregnant women. Hallmarks of preeclampsia are hypertension, proteinuria, and incomplete modification of endometrial spiral arteries. Transient proangiogenic lymphocytes called uterine natural killer (uNK) cells are implicated in human and rodent spiral artery modification. We studied mid-to late gestations in spontaneously type 1 diabetic NOD mice to investigate whether diabetes alters uNK cell homing and/or function.RESEARCH DESIGN AND METHODS-Normoglycemic, prediabetic, and diabetic NOD mice and controls were mated. Lymphocytes and endometrial endothelium and decidua were studied histologically and in functional assays.RESULTS-Conception accelerated progression to overt diabetes in NOD females who had limited spiral artery development, heavier placentas, and lighter fetuses displaying numerous birth defects compared with controls. UNK cell numbers were reduced in the decidua basalis of diabetic females, whereas interferon-␥ production was elevated. In diabetic NOD mice, decidual expression of the mucosal vascular addressin cell adhesion molecule (MAdCAM)-1 was aberrant in position, whereas vascular cell adhesion molecule (VCAM)-1 expression was reduced. Assays of lymphocyte adhesion to tissue sections under shear forces indicated that diabetes compromises the potential homing functions of both endometrial endothelium and peripheral NK cells.CONCLUSIONS-In diabetes, gestational endometrium has immune and vascular defects that likely contribute to murine fetal loss and birth defects. Analogous problems and preeclampsia in diabetic women may involve similar mechanisms. Diabetes

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Immunocytochemical Studies of Adhesion Molecules on Mouse UNK Cells and Their Extracellular Matrix Ligands During Mouse Pregnancy

Zavan

Paffaro

Joazeiro

et al. 2010

The Anatomical Record

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Uterine natural killer (uNK) cells are the dominant lymphocytes of pregnant mammals' uterus. Studies have identified four differentiation stage of mouse uNK cells based on Dolichos biflorus lectin cytochemistry, and their distribution showed preferential domain in the uterus through out the pregnancy. This work was done to investigate the expression of alpha5, alpha6, and beta7 integrins on uNK cells and their ligands distribution. Section of mouse uterus from sixth to seventeenth gestational days were submitted to immunocytochemistry and positive reactions for alpha5, alpha6, and beta7 integrins were found on uNK from eighth to tenth gestational days but not after twelfth gestational days. Fibronectin reactions were seemed from sixth to tenth gestational days around uNK from the myometrium and endometrium close to the myometrium. No reaction for fibronectin was seen in the decidualized and nondecidualized endometrium near the placenta. Laminin reaction was seen just in the antimesometrial side. beta7 integrin seems to be the active receptor to bind with VCAM-1 or MAdCAM-1 of endothelial cells, promoting the uNK cross through the vessels. The absence of laminin in an uNK domain suggests these cells are not dependent of laminin and alpha6 integrin for their establishment. However, fibronectin seems to support uNK migration, proliferation, differentiation, and survival in the uterus by binding with alpha5 integrin. The loss of alpha5 integrin ligation by the down regulation of fibronectin could inhibits these events and further studies are need to investigate whether unligated alpha5 can actively and initiate apoptosis, maybe in a caspase 8-dependent way that has been called integrin-mediated death.

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Evidence of specialized leukocyte-vascular homing interactions at the maternal / fetal interface

Cited by 65 publications

References 31 publications

Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

Immunocytochemical Studies of Adhesion Molecules on Mouse UNK Cells and Their Extracellular Matrix Ligands During Mouse Pregnancy

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