A Novel Hemocyte-Derived Peptide and Its Possible Roles in Immune Response of Ciona intestinalis Type A.

A wide variety of bioactive peptides have been identified in the central nervous system and several peripheral tissues in the ascidian Ciona intestinalis type A (Ciona robusta). However, hemocyte endocrine peptides have yet to be explored. Here, we report a novel 14-amino-acid peptide, CiEMa, that is predominant in the granular hemocytes and unilocular refractile granulocytes of Ciona. RNA-seq and qRT-PCR revealed the high CiEma expression in the adult pharynx and stomach. Immunohistochemistry further revealed the highly concentrated CiEMa in the hemolymph of the pharynx and epithelial cells of the stomach, suggesting biological roles in the immune response. Notably, bacterial lipopolysaccharide stimulation of isolated hemocytes for 1-4 h resulted in 1.9- to 2.4-fold increased CiEMa secretion. Furthermore, CiEMa-stimulated pharynx exhibited mRNA upregulation of the growth factor (Fgf3/7/10/22), vanadium binding proteins (CiVanabin1 and CiVanabin3), and forkhead and homeobox transcription factors (Foxl2, Hox3, and Dbx) but not antimicrobial peptides (CrPap-a and CrMam-a) or immune-related genes (Tgfbtun3, Tnfa, and Il17-2). Collectively, these results suggest that CiEMa plays roles in signal transduction involving tissue development or repair in the immune response, rather than in the direct regulation of immune response genes. The present study identified a novel Ciona hemocyte peptide, CiEMa, which paves the way for research on the biological roles of hemocyte peptides in chordates.

Possible roles of human mast cells in the formation of xanthelasma palpebrarum.

Cutaneous xanthoma consist of foam cells that originate from monocytes or macrophages and accumulate in perivascular areas of the skin. The main component of these cells is oxidized low-density lipoprotein (oxLDL). In this study, we show that mast cells surround the accumulated foam cells, suggesting their involvement in xanthoma formation. Coculture of THP-1 or U937 monocytes with the human mast cell line LUVA upregulated their uptake of oxLDL. Positive staining for intracellular cell adhesion molecule-1 (ICAM-1) at the borders between mast cells and foam cells was seen in pathological specimens of the most common cutaneous xanthoma, xanthelasma palpebrarum, and in cocultures. In the latter, ICAM1 messenger RNA levels were upregulated. The administration of anti-ICAM-1 blocking antibody inhibited the increase in oxLDL uptake by THP-1 or U937 monocytes cocultured with LUVA. Taken together, these results suggest a role for mast cells in the formation of xanthelasma palpebrarum and the involvement of ICAM-1 in this process.

Decidualization of Stromal Cells Promotes Involvement of Mast Cells in Successful Human Pregnancy by Increasing Stem Cell Factor Expression.

Decidualization of endometrial stromal cells and the presence of immunocompetent cells, including human mast cells, play important roles in the establishment of pregnancy. In the present study, the effects of decidualization of endometrial stromal cells on the function of decidual mast cells were elucidated. The in vitro assay revealed that decidualization of an endometrial stromal cell line, T HESCs, increased stem cell factor (SCF) mRNA expression. Decidualization of T HESCs enhanced the production of leukemia inhibitory factor (LIF), and the migration of LAD2 cells when co-cultured with T HESCs and LAD2 cells. In addition, decidualization of T HESCs enhanced cell migration in a human trophoblast cell line, HTR-8/SVneo, increased CD9 expression, a marker for extravillous trophoblast (EVT) differentiation, and decreased the secretion of ß human chorionic gonadotropin (hCG), a marker for syncytiotrophoblast (ST) differentiation, when co-cultured with T HESCs, LAD2 cells, and HTR-8/SVneo cells, in a LIF-dependent manner. Histological samples from uterine pregnancies, including decidual stromal cells, showed increased SCF mRNA expression, mast cell numbers and LIF mRNA expression thereof compared with tubal pregnancy. SCF produced by decidual stromal cells enhanced the migration and LIF production of mast cells, and promoted the migration and differentiation of trophoblasts to increase the likelihood of successful human pregnancy.