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

Abstract

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.

Common polymorphisms in the P-selectin gene in women with recurrent spontaneous abortions

“…Among these, three common variants affecting P-selectin levels -2123G>C (rs1800807), -1969G>A (rs1800805) and N562D/C-2123G (rs6127) were reported (Barbaux et al, 2001), and were investigated here. Association of these variants with RPL was reported in some, but not in all studies (Fernekorn et al, 2004;Tometten et al, 2006). To the best of our knowledge, this is the first report that investigates the association of these polymorphisms in a North-African population.…”

Monocyte Recruitment, Activation, and Function in the Gut-Associated Lymphoid Tissue during Oral Salmonella Infection

“…Blood lymphocytes express the MAdCAM-1 ligands ␣ 4 ␤ 7 integrin and CD62L, the former mediating homing to PP and the latter to peripheral lymph nodes (65). Because monocytes and neutrophils express CD62L and monocytes also express ␣ 4 ␤ 7 (37,54,55), we tested the role of MAdCAM-1 in monocyte and neutrophil recruitment to PP during oral Salmonella infection. However, normal recruitment of these cells was apparent when MAdCAM-1 was blocked.…”

“…5D) and the ␣ 4 integrin (37,54,55). CD62L and ␣ 4 partnered with ␤ 7 , in particular, are ligands for MAdCAM-1.…”

Role of Dendritic Cells in the Regulation of Maternal Immune Responses to the Fetus During Mammalian Gestation

“…The cells can further be subdivided into two subsets: CD11b + α4β7 + cells (formerly called Mac-1 + β7 + cells), and CD11b -α4β7 + (formerly called Mac-1 − β7 + cells) (Fernekorn, 2004). Chronic administration of blocking antibodies against MAdCAM-1 in wild-type mice and P-selectin −/− mice, respectively, or experimental approaches with mice deficient in P-selectin or β7-integrin revealed that this unusual expression pattern has a critical impact on the recruitment of CD11b + α4β7 + cells, whereas the mechanisms underlying the extravasation of CD11b -α4β7 + leukocytes are still ill-defined ( Figure 2) (Fernekorn, 2004).…”