Involvement of CD44 in mast cell proliferation during terminal differentiation

Abstract

By using the recently established culture system that reproduces the terminal differentiation process of connective tissuetype mast cells, we found significant transcriptional induction of CD44. As CD44 is a primary receptor for hyaluronan (HA), which is one of the major extracellular matrix components, we investigated the role of CD44 in cutaneous mast cells. When co-cultured with fibroblasts, mouse bone marrow-derived cultured mast cells (BMMCs) were found to form clusters in an HA-dependent manner. As compared with BMMCs derived from the wild-type mice, those from the CD44 À/À mice exhibited impaired growth during the co-cultured period. Furthermore, in the peritoneal cavities and ear tissues, mature mast cells were fewer in number in the CD44 À/À mice than in the wild-type mice. We investigated roles of CD44 in mast cell proliferation by reconstituting BMMCs into the tissues of mast cell-deficient, Kit W /Kit W-v mice, and found that the number of metachromatic cells upon acidic toluidine blue staining in the tissues transplanted with CD44 À/À BMMCs was not significantly changed for 10 weeks, whereas that in the tissues transplanted with the CD44 þ / þ BMMCs was significantly increased. These results suggest that CD44 plays a crucial role in the regulation of the cutaneous mast cell number. As heterogeneity of tissue mast cells arise as a result of differences in the microenvironment that affects the process of the terminal differentiation, extensive investigation of the maturation process is required for precise understanding of the roles of tissue mast cells. Although several mast cell lines and IL-3-dependent bone marrow-derived cultured mast cells (BMMCs) have been used as models to investigate the process of mast cell activation and subsequent production of proinflammatory mediators, these models have limitations in analyzing functions specific to mature mast cells. Hence, recent studies have often employed the mast cell knock-in models using the mast cell-deficient mice, such as WBB6F1-) and C57BL/6-Kit), to investigate the roles of mature mast cells in vivo.1 By modifying the co-culturing method of BMMCs together with fibroblasts in the presence of stem cell factor (SCF), we have recently established a culture system for development of mature mast cells, which exhibit properties characteristic of connective tissue-type mast cells (CTMCs), such as degranulation induced by cationic secretagogues, Safranin-positive granules, and high levels of mast cell protease expression. 4 We then investigated the gene expression profile during the culture period and identified a cluster of candidate genes, which have potentials to modulate mast cell

CD44 in hematological neoplasias

“…Similarly Langerhans and dendritic cell migration is mediated at least in parts by CD44, since antibodies against CD44 block OPN-induced cell migration to lymphatic organs in mice [89]. Also the proliferation of mast cells is regulated by CD44 [90].…”

Impaired activation of mast cells upon IgE-mediated antigen stimulation in a stroke-prone spontaneously hypertensive rat strain, SHRSP.Z

“…The lysate was centrifuged at 10,000 × g for 30 min at 4 • C. Activities of three different types of granule proteases and histamine content in the resultant supernatants were measured as previously described [8,9].…”

“…Surface expression of FcRI in peritoneal cells was measured using FACSCalibur (Becton Dickinson) equipped with CELLQUEST software as described previously [8].…”

Role of versican V0/V1 and CD44 in the regulation of human melanoma cell behavior

“…CD44 can also interact with the cytoskeletal proteins through its cytoplasmic domain. All these interactions allow CD44 to play an important role in tumor progression by enhancing cell proliferation, adhesion, migration and invasion (23)(24)(25)(26)(27)(28). Furthermore, it has a central function in HA metabolism, since it has a central role in HA internalization (29,30).…”