Regulation of leukocyte recruitment to the murine maternal/fetal interface by specialized patterns of vascular adhesion receptors

Our findings reveal a remarkable regulation of leukocyte recruitment to specialized microdomains at the maternal/fetal interface during initial placenta development. Each of these microdomains is associated with unique patterns of vascular differentiation, including distinctive populations of leukocytes. A striking observation is the coexpression of the a4b7 ligand MAdCAM-1 and P-selectin on vessels of the vascular zone within the decidua basalis. This combination may restrict interactions to leukocytes combining the unusual ability to bind P-selectin and MAdCAM-1 (e.g. a4b7+ monocytes observed in these vessels). The maternal vessels of the central decidua basalis surrounded by a4b1+ uNK cells express the a4b1 ligand VCAM-1. To assess directly the importance of identified vascular adhesion receptors TRITC-labeled a4b7hi TK1 or a4b1+ L1/2 cells were injected i.v. and allowed to circulate for 1 hr. Then the uterus was sectioned to identify vascular sites of accumulation. TK1 cells were localized in the MAdCAM-1 + P-selectin+ vessels of the vascular zone whereas L1/2 cells interacted selectively with vessels in the central decidua basalis. Prior injection of blocking mABs against MAdCAM-1 or VCAM-1 inhibited accumulation of TK1 cells or L1/2 cells, respectively. Long-term inhibition studies using blocking mABs against MAdCAM-1, P-selectin or a4b7 integrin as well as experiments with b7ko mice suggest a critical role of a4b7+ monocytes for the differentiation of uNK cells and placentation.