Immune Characterization of Bone Marrow-Derived Models of Mucosal and Connective Tissue Mast Cells

PURPOSE: It is well appreciated that mast cells (MCs) demonstrate tissue-specific imprinting, with different biochemical and functional properties between connective tissue MCs (CTMCs) and mucosal MCs (MMCs). Although in vitro systems have been developed to model these different subsets, there has been limited investigation into the functional characteristics of the 2 major MC subsets. Here, we report the immunologic characterization of 2 MCs subsets developed in vitro from bone marrow progenitors modeling MMCs and CTMCs. METHODS: We grew bone marrow for 4 weeks in the presence of transforming growth factor (TGF)-β, interleukin (IL)-9, IL-3, and stem cell factor (SCF) to generate MMCs, and IL-4, IL-3, and SCF to generate CTMCs. RESULTS: CTMCs and MMCs differed in growth rate and protease content, but their immune characteristics were remarkably similar. Both subsets responded to immunoglobulin E (IgE)-mediated activation with signaling, degranulation, and inflammatory cytokine release, although differences between subsets were noted in IL-10. CTMCs and MMCs showed a similar toll-like receptor (TLR) expression profile, dominated by expression of TLR4, TLR6, or both subsets were responsive to lipopolysaccharide (LPS), but not poly(I:C). CTMCs and MMCs express receptors for IL-33 and thymic stromal lymphopoietin (TSLP), and respond to these cytokines alone or with modified activation in response to IgE cross-linking. CONCLUSIONS: The results of this paper show the immunologic characterization of bone marrow-derived MMCs and CTMCs, providing useful protocols for in vitro modeling of MC subsets.

New era for mucosal mast cells: their roles in inflammation, allergic immune responses and adjuvant development

To achieve immune homeostasis in such a harsh environment as the intestinal mucosa, both active and quiescent immunity operate simultaneously. Disruption of gut immune homeostasis leads to the development of intestinal immune diseases such as colitis and food allergies. Among various intestinal innate immune cells, mast cells (MCs) play critical roles in protective immunity against pathogenic microorganisms, especially at mucosal sites. This suggests the potential for a novel MC-targeting type of vaccine adjuvant. Dysregulated activation of MCs also results in inflammatory responses in mucosal compartments. The regulation of this yin and yang function of MCs remains to be elucidated. In this review, we focus on the roles of mucosal MCs in the regulation of intestinal allergic reaction, inflammation and their potential as a new target for the development of mucosal adjuvants.

Somatostatin suppressed the activity of intestinal mucosal mast cells in rats with multiple organ failure / 中华消化杂志

Objective To investigate the effect of somatostatin(SST) on the activity of intestinal mucosal mast cells(IMMC) and its pathological significance in the development of multiple organ failure(MOF). Methods The rat model of MOF was established by the peritoneal injection of zymosan. Thirty minutes after the injection of zymosan, SST at 2.300 ng?kg -1 ?h -1 or 0.023 ng?kg -1 ?h -1 was injected respectively through tail veins. The concentration of histamine and tumor necrosis factor-? (TNF-?) in plasma and intestinal tissue were measured. The pathological alterations of essential organ including intestine, liver, kidney, lung and heart were studied under light microscope. Their corresponding functions were reflected with alanine aminotransferase (ALT), cretinine (Cr) and oxygen pressure (PO 2). In addition, the ultra structure of the IMMC was observed under a transmission electronic microscope. Results Compared with the controlled rats, the rats injected with SST (2.300 ng?kg -1 ?h -1 ) showed less serious inflammatory response under light microscope. ALT and Cr were decreased 53% and 60% respectively. However, the lung ventilation was improved and PO 2 was increased by 50%. The histamine level in the intestinal tissue from rats treated with SST remarkably increased( ( 8.60? 0.50 ) ng/g protein to ( 14.50? 1.08 ) ng/g protein), whilst the plasma histamine level did not show any significant changes. Exogeneous SST also resulted in lower level of TNF-? in intestine but no changes in plasma. Furthermore, degranulation of IMMC from the rats treated with SST was less obvious. Conclusion SST may prevent from or arrest the development of MOF through suppression of the release of inflammatory mediators, such as histamine and TNF-?.

Effects of gut peptides on the activation of mast cells from rat intestinal mucosa in vitro / 中国免疫学杂志

Objective:To investigate the effects of substance P(SP),somatostain(SST) and vasoactive intestinal peptide(VIP) on the activation of rat intestinal mucosal mast cells(IMMC) in vitro.Methods:IMMC isolated and purified from the whole intestines of normal rats were incubated with gut peptides at various concentrations.The histamine concentration in IMMC and their supernate were determined.Furthermore,the ultrastructure of the incubated IMMC was observed under a transmission electronic microscope.Results:①The spontaneous release rate of histamine was (22.86?3.22)%.②SP significantly increased the histamine release rate from IMMC(P0.05)④At the concentration from 1?10 -1 mol/L to 1?10 -8 mol/L,the higher concentration of VIP was used,the lower histamine release rate was observed(P

Effects of substance P on the activity of intestinal mucosal mast cells in rats with multiple organ failure / 中华消化杂志

Objective Multiple organ failure (MOF) has been regarded as a continuous, uncontrolled inflammatory response. Intestinal mucosal mast cells (IMMC) may be involved in MOF. Substance P (SP), one of gut peptides, is an important regulator in the neuro-endocrine-immune network. However, the effects of SP on IMMC, especially in the case of MOF, remain unclear. This study was aimed to investigate the effects of SP on IMMC in the development of MOF. Methods The rat model of MOF was established by injecting zymosan. After thirty minutes of the injection, SP was given through tail veins at the dose of 20 nmol/kg weight and 0.2 nmol/kg weight. The concentrations of histamine and tumor necrosis facfor-?(TNF-?) in plasma and intestine tissues were measured. The pathological alterations of essential organs including intestine, liver, kidney and lung were examined under light microscope. Their corresponding functions were reflected with ALT, Cr and PO 2. The ultrastructure of the IMMC was also observed under a transmission electronic microscope. Results Compared with the controlled rats, those injected with SP showed much more serious inflammatory response under light microscope. Both ALT and Cr increased by about 50%, but PO 2 decreased by about 40%. Histamine level in the intestinal tissue of the rats treated with SP remarkably decreased, whereas the plasma histamine level did not show any significant changes. The level of TNF-? was higher in the intestinal tissue of the rats treated with SP but no change in plasma, and the degranulation of IMMC under transmission electronic microscope was more obvious.Conclusions SP may trigger MOF through acting on IMMC which may release inflammatory mediators such as histamine and TNF-?.