No abstract

SummaryThe effect of nerve growth factor (NGF) on proliferation/differentiation of mast cells was investigated in vitro. Although NGF alone neither supported colony formation of bone marrow-derived cultured mast cells (BMCMC) nor induced development of mast cell colonies from nonadherent bone marrow cells (NBMC), addition of NGF to the suboptimal dose of interleukin 3 (IL3) significantly increased the numbers of mast cell colonies produced by BMCMC or NBMC in methylcellulose. When stimulated by IL3 alone, cells in mast cell colonies were not stained by berberine sulfate, a fluorescent dye. In contrast, mast cells developing in methylcellulose cultures obtaining both 11,3 and NGF were stained by berberine sulfate. The fluorescence was abolished by the treatment of heparinase but not of chondroitinase ABC, suggesting that mast cells stimulated by 11,,3 and NGF produced and stored heparin proteoglycan . The histamine content of BMCMC maintained by IL-3 was also increased by addition of NGF. Since BMCMC showed mucosal mast cell-like phenotype, NGF appeared to induce the phenotypic change to connective tissue-type mast cells (CTMC) . In the culture containing BMCMC, 3T3 fibroblasts, and IL-3, the phenotypic change of BMCMC to CTMC was observed as well . Since NGF was detected in this coculture and since addition of anti-NGF monoclonal antibody suppressed the phenotypic change, NGF produced by fibroblasts appeared to induce the phenotypic change. Neither BMCMC alone nor IL3 alone increased the concentration of NGF. Therefore, there is a possibility that BMCMC stimulated by IL3 may induce the production and/or release of NGF by fibroblasts .

No abstract

Natural killer (NK) cells become a prominent cell population in the rodent uterus during pregnancy. The mature, heavily granulated form of these cells is rare in virgin or postpartum uteri. Death, migration, or dedifferentiation could account for the disappearance of these cells from late gestation uteri. We asked whether uterine NK cells, also known as granulated metrial gland (GMG) cells, die in situ and if expression of Fas antigen is essential for their death. Late in gestation, fragmentation of nuclear DNA was detected histologically by OH-end labeling, as were ultrastructural changes suggesting cell death. NK cells developed in and were lost from the uteri of pregnant Fas antigen-deficient lpr/lpr mice. Postpartum samples of retained placentas contained some residual NK cells that had moved from regions of uterine musculature toward the uterine lumen and were being expelled with the placenta. Thus, both cell death and placental separation remove NK cells from the peripartum uterus.

The metrial gland develops in the uterus of many rodent species during normal pregnancy. It is a maternally-derived tissue that contains stromal and vascular elements plus a population of large cells, striking in their light microscopic appearance due to the presence of numerous cytoplasmic granules. These cells, which have become known in mice and rats as granulated metrial gland (GMG) cells, are derived from bone marrow precursors and recent work suggests they are a subset of lymphocytes belonging to the natural killer (NK) cell lineage. The functions of GMG cells during normal gestation have not been clearly defined. In vitro, GMG cells have been shown to produce cytokines and their cytokine profile is altered upon addition of medium containing the T cell growth factor interleukin-2 (IL-2). GMG cell granules contain the cytolytic protein perforin but GMG cells have a very limited capacity to kill in vitro unless they have been stimulated by IL-2 or interferon-gamma. Histological study of GMG cells has suggested they preferentially associate with fetal trophoblast. Since trophoblast appears resistant to immune lysis, except by IL-2-activated effector lymphocytes, and because resorbing murine embryos become infiltrated by lytic cells of the NK cell lineage, it is important to establish whether GMG cells are activated by pregnancy-associated events to play a major lytic role in vivo.