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.
Adjuvants, Immunologic/*therapeutic use ; Animals ; Humans ; Hypersensitivity/*immunology/prevention & control ; Inflammation/immunology/metabolism/prevention & control ; Intestinal Mucosa/cytology/*immunology ; Mast Cells/*immunology

Mast cells have been regarded for a long time as effector cells in IgE mediated type I reactions and in host defence against parasites. However, they are resident in all environmental exposed tissues and express a wide variety of receptors, suggesting that these cells can also function as sentinels in innate immune responses. Indeed, studies have demonstrated an important role of mast cells during the induction of life-saving antibacterial responses. Furthermore, recent findings have shown that mast cells promote and modulate the development of adaptive immune responses, making them an important hinge of innate and acquired immunity. In addition, mast cells and several mast cell-produced mediators have been shown to be important during the development of allergic airway diseases. In the present review, we will summarize findings on the role of mast cells during the development of adaptive immune responses and highlight their function, especially during the development of allergic asthma.
Animals ; Anti-Infective Agents/pharmacology ; Asthma/*immunology/metabolism ; Cytokines/metabolism ; Histamine/metabolism ; Humans ; Hypersensitivity/*immunology/metabolism ; Immune System ; Immunoglobulin E/immunology ; Leukotrienes/metabolism ; Mast Cells/*cytology ; Mice ; Models, Biological ; Prostaglandins/metabolism ; Tumor Necrosis Factor-alpha/metabolism

This study was performed in order to assess whether acute stress can increase mast cell and enterochromaffin (EC) cell numbers, and proteinase-activated receptor-2 (PAR2) expression in the rat colon. In addition, we aimed to investigate the involvement of corticotrophin-releasing factor in these stress-related alterations. Eighteen adult rats were divided into 3 experimental groups: 1) a saline-pretreated non-stressed group, 2) a saline-pretreated stressed group, and 3) an astressin-pretreated stressed group. The numbers of mast cells, EC cells, and PAR2-positive cells were counted in 6 high power fields. In proximal colonic segments, mast cell numbers of stressed rats tended to be higher than those of non-stressed rats, and their PAR2-positive cell numbers were significantly higher than those of non-stressed rats. In distal colonic segments, mast cell numbers and PAR2-positive cell numbers of stressed rats were significantly higher than those of non-stressed rats. Mast cell and PAR2-positive cell numbers of astressin-pretreated stressed rats were significantly lower than those of saline-pretreated stressed rats. EC cell numbers did not differ among the three experimental groups. Acute stress in rats increases mast cell numbers and mucosal PAR2 expression in the colon. These stress-related alterations seem to be mediated by release of corticotrophin-releasing factor.
Animals ; Colon/*metabolism ; Corticotropin-Releasing Hormone/antagonists & inhibitors/metabolism/pharmacology/*physiology ; Enterochromaffin Cells/cytology ; Male ; Mast Cells/*cytology/immunology/metabolism ; Peptide Fragments/pharmacology ; Rats ; Rats, Wistar ; Receptor, PAR-2/*metabolism ; Restraint, Physical ; *Stress, Physiological

Mucosal mast cell-derived chondroitin sulphates (sulphated proteoglycans) were assayed in gut washings and homogenate of FcRgamma-knockout (KO) and wild-type (WT) C57BL/6 mice challenged with Strongyloides venezuelensis in order to assess their possible role in secondary immunity against enteric nematodes. Groups of immune KO and WT mice were challenged by oral gavage with 300 infective larvae (L3). Establishment of infection was assessed by daily faecal analysis to determine the number of eggs per gram of faeces (EPG) and by adult worm recovery on days 5 and 13 post challenge. Mucosal mast cell (MMC) counts were done on days 5 and 13 post challenge while MMC-derived chondroitin sulphates in gut washings (days 1 and 5) and homogenate (day 8) were assayed by high performance liquid chromatography (HPLC). Results showed that patent infection occurred in challenged KO but not WT mice despite significantly higher mastocytosis in jejunal sections of KO than WT mice (p<0.001). Similarly but against prediction, significantly higher concentration of MMC-derived chondroitin sulphates was observed in gut homogenate of KO than WT mice (p<0.05). In contrast, significantly higher concentration of chondroitin sulphates was observed in gut washings of WT than KO mice (p<0.05). These results suggest that MMC in KO mice failed to release sufficient amount of sulphated proteoglycans into the gut lumen as did the WT mice, which may have been part of the hostile environment that prevented the establishment in and eventual expulsion of adult S. venezuelensis from the gut of WT mice following challenge.
Animals ; Cell Count/veterinary ; Chondroitin Sulfates/*immunology/metabolism ; Chymases ; Feces/parasitology ; Intestinal Diseases, Parasitic/immunology/*veterinary ; Intestinal Mucosa/cytology/immunology/parasitology ; Jejunum/cytology/immunology/parasitology ; Male ; Mast Cells/immunology/metabolism/*parasitology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Parasite Egg Count/veterinary ; Receptors, IgG/*immunology ; Serine Endopeptidases/blood/immunology ; Specific Pathogen-Free Organisms ; Strongyloides/*immunology ; Strongyloidiasis/immunology/parasitology/*veterinary

OBJECTIVETo establish a new, real time, dynamic and direct optical detection method for mast cell degranulation caused by anaphylactoid reaction.

METHODA CD63-GFP plasmid was constructed and introduced steadily into rat basophilic leukemia (RBL-2H3) cells. The movements of CD63-GFP, which was located on both the granule membranes and the plasma membranes of RBL cells stimulated by Compound 48/80, were studied by confocal laser scanning microscope (CLSM) and total internal reflection fluorescence microscope (TIRFM) both inside and on the surface of living RBL-2H3 cells.

RESULTBefore antigen stimulation, most granules with CD63-GFP hardly moved in RBL cells. However, after antigen stimulation, the granules moved dramatically. They reached the plasma membranes in a few minutes and fused with them instantaneously. The velocity of the granule movement toward the plasma membranes on antigen stimulation was calculated to be 0.05 micron x s(-1).

CONCLUSIONAnalysis of the movement of each granule provided a new insight into the elementary process of degranulation. The method is rapid, sensitive and reliable, which could be used as a new detection method for anaphylactoid reaction in vitro.

Anaphylaxis ; diagnosis ; immunology ; metabolism ; Animals ; Antigens, CD ; genetics ; Cell Degranulation ; Cell Line, Tumor ; Cell Movement ; Mast Cells ; cytology ; immunology ; Microscopy, Confocal ; Microscopy, Fluorescence ; Platelet Membrane Glycoproteins ; genetics ; Rats ; Tetraspanin 30 ; Time Factors

BACKGROUNDMast cells are implicated in the development of irritable bowel syndrome (IBS), which is associated with the activation of the "neural-immune" system. The aim of this study was to investigate the role of mast cells in the remodeling of cholinergic and peptidergic neurotransmitters induced by acute cold restriction stress (ACRS) post infection (PI) using mast cell deficient rats (Ws/Ws) and their wild-type controls (+/+).

METHODSTransient intestinal infection was initiated by giving 1500 Trichinella spiralis (T.S.) larvae by gavage. ACRS was induced for 2 hours at day 100 PI. Samples of terminal ilea were prepared for H&E staining, mast cell counting and activation and assessment of IL-1beta and IL-10.

RESULTSWhen infected, both strains of rats experienced an acute infectious stage followed by a recovery. Histological scores were significantly higher in infected rats compared with those of the non-infected controls at day 10 PI (10 day-PI vs. control: +/+: 2.75+/-0.17 vs. 0.42+/-0.09; Ws/Ws: 2.67+/-0.67 vs. 0.50+/-0.34; P<0.01). In +/+ rats, post-infection ACRS induced the formation of low-grade inflammation, represented by the imbalance of IL-1beta and IL-10 (IL-1beta: PI+ACRS vs. control: (1812.24+/-561.61) vs. (1275.97+/-410.21) pg/g, P<0.05; IL-10: PI+ACRS vs. control: (251.9+/-39.8) vs. (255.3+/-24.7) pg/g, P>0.05), accompanied by hyperplasia and activation of mast cells (PI+ACRS vs. control: 58.8+/-19.2 vs. 28.0+/-7.6; P<0.01). The balance between acetylcholine (ACh) and substance P (SP) was also disturbed (ACh: PI+ACRS vs. control: (743.94+/-238.72) vs. (1065.68+/-256.46) pg/g, P<0.05; SP: PI+ACRS vs. control: (892.60+/-231.12) vs. (696.61+/-148.61) pg/g, P<0.05). Nevertheless, similar changes of IL-1beta/IL-10 and ACh/SP were not detected in Ws/Ws rats.

CONCLUSIONThe imbalance of ACh/SP, together with the activation of mucosal immunity induced by post-infection ACRS were lacking in mast cell deficient rats, which supports the premise that mast cells play an important role in cholinergic and peptidergic remodeling in the ileum of rats.

Acetylcholine ; metabolism ; Animals ; Enzyme-Linked Immunosorbent Assay ; Ileum ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-1beta ; metabolism ; Intestines ; immunology ; metabolism ; parasitology ; Male ; Mast Cells ; cytology ; metabolism ; physiology ; ultrastructure ; Microscopy, Electron, Transmission ; Neurotransmitter Agents ; metabolism ; Radioimmunoassay ; Rats ; Substance P ; metabolism ; Trichinella spiralis ; physiology ; Trichinellosis ; immunology