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Selectin, Platelet Plays a Critical Role in Granulocyte Access to the Pregnant Mouse Uterus Under Physiological and Pathological Conditions¹

Institute of Immunology and Transfusion Medicine,³ University of Lübeck, 23538 Lübeck, Germany Laboratory of Immunology and Vascular Biology,⁴ Department of Pathology, Stanford University School of Medicine, Stanford, California 94305

ABSTRACT

Leukocyte recruitment to the pregnant mouse uterus is associated with highly regulated patterns of expression of vascular adhesion receptors. One striking observation is the localized expression of mucosal vascular addressin cell adhesion molecule (MADCAM1) and selectin, platelet (SELP, formerly P-selectin) by maternal vessels in the vascular zone (VZ) during the first half of pregnancy. From midgestation onwards, endothelial cells lining the maternal vessels of the VZ in addition express vascular cell adhesion molecule-1 (VCAM1). The predominant cell population within these vessels is monocyte-like cells. Granulocytes and low numbers of lymphocytes are also present. Murine fetal trophoblast cells are almost devoid of adhesion molecules, including SELP. In contrast, spontaneous abortions of allogeneic pregnancies are characterized by dramatic upregulation of SELP on maternal VZ vessels and on fetal trophoblast cells. Upregulation of SELP is associated with a dramatic influx of highly activated granulocytes, which infiltrate the vessels and tissue of the VZ and the trophoblast. The majority of the activated granulocytes within the trophoblast undergo nuclear fragmentation, which can be detected by TUNEL staining. To demonstrate that SELP is involved in the recruitment of granulocytes to the pregnant uterus, we undertook long-term in vivo inhibition studies using a monoclonal antibody to inhibit the contribution of SELP to leukocyte trafficking to the decidua. In addition, the pregnant uteri of syngeneic Selp^–/– x Selp^–/– mice were investigated and compared to the controls. Our results clearly demonstrate the importance of SELP for granulocyte access to the pregnant mouse uterus under physiological and pathological conditions.

decidua, female reproductive tract, immunology, trophoblast, uterus

¹Supported by grant GRK288C5 from the Deutsche Forschungsgemeinschaft (DFG).

Correspondence: ²Andrea Kruse, Institute of Immunology and Transfusion Medicine, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. FAX: 49 451 5002857; e-mail: kruse{at}immu.mu-luebeck.de