A study on the density and distribution of uterine Natural Killer cells at mid pregnancy in mice genetically-ablated for CCR2, CCR 5 and the CCR5 receptor ligand, MIP-1α

Several chemoattractants mediate Natural Killer (NK) cell migration. The CC-chemokines, monocyte inflammatory protein (MIP)-1 alpha, regulated upon activation, normal T cell expressed and secreted (RANTES) and macrophage chemotactic protein (MCP)-1 are the most potent. Peripheral NK cells express the CC-chemokine receptor CCR2, for MCP-1 and CCR5, for MIP-1 alpha and RANTES. These chemokines are detected in the uterus during the estrous cycle and become elevated during pregnancy. To assess the roles of CCR2, CCR5 and MIP-1 alpha in NK cell migration to the uterus and localization within implantation sites, histological analysis was conducted on implantation sites from mice genetically-ablated for CCR2, CCR5, MIP-1 alpha or CCR2 and MIP-1 alpha. Uterine NK (nNK) cell densities in both the decidua basalis and mesometrial lymphoid aggregate of pregnancy (MLAp) of all mutant strains matched wildtype controls. Ratios of vascular: Iron-vascular uNK cell position were identical in mutants and controls. In the decidua basalis, 25-35% and in the MLAp, 15-20% of uNK cells were perivascular. Intravascular uNK cells were observed in the decidua basalis but not in the MLAp and were more numerous at gestation day 10 than 12. Two measures of uNK cell activation, cell diameter and cytoplasmic granule number, were similar in the mutants and controls. Thus. migration, distribution and activation of NK cells within the pregnant uterus are independent of CCR2, CCR5 and MIP-1 alpha. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.