scholarly journals Brain Mast Cells Act as an Immune Gate to the Hypothalamic-Pituitary-Adrenal Axis in Dogs

2001 ◽  
Vol 194 (1) ◽  
pp. 71-78 ◽  
Author(s):  
Itsuro Matsumoto ◽  
Yasuhisa Inoue ◽  
Toshio Shimada ◽  
Tadaomi Aikawa
Keyword(s):  
Mast Cells ◽  
Host Defense ◽  
Bacterial Infections ◽  
Immunoglobulin E ◽  
Intravenous Route ◽  
Pars Tuberalis ◽  
Type I ◽  
Cortisol Secretion ◽  
Hypothalamic Pituitary Adrenal ◽  
H2 Blocker

Mast cells perform a significant role in the host defense against parasitic and some bacterial infections. Here we show that in the dog, degranulation of brain mast cells evokes hypothalamic-pituitary-adrenal responses via histamine release. A large number of mast cells were found in a circumscribed ventral region of the hypothalamus, including the pars tuberalis and median eminence. When these intracranial mast cells were passively sensitized with immunoglobulin E via either the intracerebroventricular or intravenous route, there was a marked increase in the adrenal cortisol secretion elicited by a subsequent antigenic challenge (whether this was delivered via the central or peripheral route). Comp.48/80, a mast cell secretagogue, also increased cortisol secretion when administered intracerebroventricularly. Pretreatment (intracerebroventricularly) with anti-corticotropin–releasing factor antibodies or a histamine H1 blocker, but not an H2 blocker, attenuated the evoked increases in cortisol. These data show that in the dog, degranulation of brain mast cells evokes hypothalamic-pituitary-adrenal responses via centrally released histamine and corticotrophin-releasing factor. On the basis of these data, we suggest that intracranial mast cells may act as an allergen sensor, and that the activated adrenocortical response may represent a life-saving host defense reaction to a type I allergy.

scholarly journals Roles of a Mast Cell–Specific Receptor MRGPRX2 in Host Defense and Inflammation

2020 ◽  
Vol 99 (8) ◽  
pp. 882-890 ◽  
Author(s):  
C. Chompunud Na Ayudhya ◽  
S. Roy ◽  
M. Thapaliya ◽  
H. Ali
Keyword(s):  
Mast Cells ◽  
Bacterial Infection ◽  
Host Defense ◽  
Immune Cells ◽  
Inflammatory Pain ◽  
Bacterial Infections ◽  
Neurogenic Inflammation ◽  
Inflammatory Diseases ◽  
Adaptive Immune Cells ◽  
Novel Approaches

Mast cells are multifunctional immune cells that are found most abundantly at host-environment interfaces, such as the skin, respiratory tract, and oral/gastrointestinal mucosa. Not surprisingly, mast cells act as sentinel cells that sense microbial attacks and initiate a protective immune response and promote healing. Although mast cells share many features with other innate immune effector cells, such as neutrophils and macrophages, they uniquely interact closely with blood vessels and release an extensive set of mediators for the recruitment of innate and adaptive immune cells. A novel human G protein-coupled receptor (GPCR), known as Mas-related GPCR-X2 (MRGPRX2, mouse ortholog, MrgprB2), has recently been identified, which is expressed on mast cells but not neutrophils and macrophages. Interestingly, activation of MrgprB2 by bacteria-derived quorum-sensing peptides inhibits bacterial growth, prevents biofilm formation, and leads to the recruitment of neutrophils to effectively clear bacteria. Furthermore, host defense antimicrobial peptides and small-molecule peptide mimetics also activate mast cells via MRGPRX2/B2. MrgprB2-mediated activation of local mast cells also clears cutaneous bacterial infection, promotes healing, and protects against reinfection. In addition to their role in host defense, mast cells contribute to a number of chronic inflammatory diseases such as periodontitis, neurogenic inflammation, and inflammatory pain likely via the activation of MRGPRX2. In this review, we discuss the roles of MRGPRX2/B2 in the clearance of bacterial infection, wound healing, periodontal disease, neurogenic inflammation, and inflammatory pain. We propose that harnessing mast cells’ host defense and immunomodulatory properties via the activation of MRGPRX2 may lead to novel approaches for the treatment of drug-resistant bacterial infections. On the other hand, increased MRGPRX2 expression on mast cells and their inappropriate activation may contribute to periodontitis, neurogenic inflammation, and inflammatory pain. Thus, targeting MRGPRX2 could provide novel approaches to modulate these conditions.

scholarly journals Hispidulin Inhibits Mast Cell-Mediated Allergic Inflammation through Down-Regulation of Histamine Release and Inflammatory Cytokines

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2131 ◽  
Author(s):  
Dong Eun Kim ◽  
Kyoung-jin Min ◽  
Min-Jong Kim ◽  
Sang-Hyun Kim ◽  
Taeg Kyu Kwon
Keyword(s):  
Mast Cells ◽  
Inflammatory Cytokines ◽  
Immunoglobulin E ◽  
Inflammatory Diseases ◽  
Allergic Inflammation ◽  
Interleukin 4 ◽  
Type I ◽  
Ige Mediated ◽  
Factor Α ◽  
Jnk Activation

Hispidulin (4′,5,7-trihydroxy-6-methoxyflavone) is a natural compound derived from traditional Chinese medicinal herbs, and it is known to have an anti-inflammatory effect. Here, we investigated the effect of hispidulin on the immunoglobulin E (IgE)-mediated allergic responses in rat basophilic leukemia (RBL)-2H3 mast cells. When RBL-2H3 cells were sensitized with anti-dinitrophenyl (anti-DNP) IgE and subsequently stimulated with DNP-human serum albumin (HSA), histamine and β-hexosaminidase were released from the cells by degranulation of activated mast cells. However, pretreatment with hispidulin before the stimulation of DNP-HSA markedly attenuated release of both in anti-DNP IgE-sensitized cells. Furthermore, we investigated whether hispidulin inhibits anti-DNP IgE and DNP-HSA-induced passive cutaneous anaphylaxis (PCA), as an animal model for Type I allergies. Hispidulin markedly decreased the PCA reaction and allergic edema of ears in mice. In addition, activated RBL-2H3 cells induced the expression of inflammatory cytokines (tumor necrosis factor-α and interleukin-4), which are critical for the pathogenesis of allergic disease, through the activation of c-Jun N-terminal kinase (JNK). Inhibition of JNK activation by hispidulin treatment reduced the induction of cytokine expression in the activated mast cells. Our results indicate that hispidulin might be a possible therapeutic candidate for allergic inflammatory diseases through the suppression of degranulation and inflammatory cytokines expression.

Degranulation of mast cells located in median eminence in response to compound 48/80 evokes adrenocortical secretion via histamine and CRF in dogs

2004 ◽  
Vol 287 (4) ◽  
pp. R969-R980 ◽  
Author(s):  
Itsuro Matsumoto ◽  
Yasuhisa Inoue ◽  
Katsuhiko Tsuchiya ◽  
Toshio Shimada ◽  
Tadaomi Aikawa
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Receptor Antagonist ◽  
Median Eminence ◽  
Close Association ◽  
Portal System ◽  
Pars Tuberalis ◽  
Cortisol Secretion ◽  
Intracerebroventricular Infusion ◽  
Arterial Blood

The effect of intracerebroventricular infusion of compound 48/80 (C48/80), a mast cell secretagogue, on adrenal cortisol secretion was investigated in dogs under pentobarbital sodium anesthesia. A marked increase in adrenal cortisol secretion was elicited by C48/80 along with a concomitant increase in the plasma levels of cortisol and immunoreactive ACTH, but neither arterial blood pressure and heart rate nor the plasma histamine level altered significantly. Pretreatment with either anti-CRF antiserum or pyrilamine maleate (H1 histamine-receptor antagonist) significantly attenuated the C48/80-evoked increase in cortisol secretion, but pretreatment with metiamide (H2-receptor antagonist) significantly potentiated it. Significant attenuation of the C48/80-evoked increase in cortisol also occurred in dogs given ketotifen, a mast cell stabilizing drug, before pharmacologic challenge. In the pars tuberalis and median eminence (ME), mast cells were highly concentrated in close association with the primary plexus of the hypophysial portal system. Degranulated mast cells were extensively found in the ME of C48/80-treated animals. These results suggest that mast cells located in these regions liberated histamine within the brain as a result of degranulation induced by C48/80 and that this led to activation of the hypothalamic-pituitary-adrenocortical axis.

scholarly journals The Response of Tissue Mast Cells to TLR3 Ligand Poly(I:C) Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Piotr Witczak ◽  
Ewa Brzezińska-Błaszczyk ◽  
Justyna Agier
Keyword(s):  
Mast Cells ◽  
Bacterial Infections ◽  
Lymphatic Vessels ◽  
Poly I:C ◽  
Type I ◽  
Viral Dsrna ◽  
Mhc I ◽  
Antiviral Immune Response ◽  
Cellular Antiviral Response

Mast cells (MCs) are found mainly at the anatomical sites exposed to the external environment; thus, they are localized close to blood vessels, lymphatic vessels, and a multitude of immune cells. Moreover, those cells can recognize invading pathogens through a range of surface molecules known as pathogen recognition receptors (PRRs), mainly Toll-like receptors (TLRs). MCs are extensively engaged in the control and clearance of bacterial infections, but much less is known about their contribution to antiviral host response as well as pathomechanisms of virus-induced diseases. In the study, we employed in vivo differentiated mature tissue mast cells freshly isolated from rat peritoneal cavity. Here, we demonstrated that rat peritoneal mast cells (rPMCs) express viral dsRNA-specific TLR3 molecule (intracellularly and on the cell surface) as well as other proteins associated with cellular antiviral response: IRF3, type I and II IFN receptors, and MHC I. We found that exposure of rPMCs to viral dsRNA mimic, i.e., poly(I:C), induced transient upregulation of surface TLR3 (while temporarily decreased TLR3 intracellular expression), type II IFN receptor, and MHC I. TLR3 ligand-stimulated rPMCs did not degranulate but generated and/or released type I IFNs (IFN-α and IFNβ) as well as proinflammatory lipid mediators (cysLTs), cytokines (TNF, IL-1β), and chemokines (CCL3, CXCL8). We documented that rPMC priming with poly(I:C) did not affect FcεRI-dependent degranulation. However, their costimulation with TLR3 agonist and anti-IgE led to a significant increase in cysLT and TNF secretion. Our findings confirm that MCs may serve as active participants in the antiviral immune response. Presented data on modulated FcεRI-mediated MC secretion of mediators upon poly(I:C) treatment suggests that dsRNA-type virus infection could influence the severity of allergic reactions.

scholarly journals Francisella novicida Mutant XWK4 Triggers Robust Inflammasome Activation Favoring Infection

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu Guo ◽  
Rudi Mao ◽  
Qingqing Xie ◽  
Xiaojie Cheng ◽  
Tao Xu ◽  
...  
Keyword(s):  
Host Defense ◽  
Bacterial Infections ◽  
Cytokine Production ◽  
Inflammatory Diseases ◽  
Inflammasome Activation ◽  
Type I ◽  
Wild Type ◽  
Francisella Novicida ◽  
Activation Type

Bacterial infection tendentiously triggers inflammasome activation, whereas the roles of inflammasome activation in host defense against diverse infections remain unclear. Here, we identified that an ASC-dependent inflammasome activation played opposite roles in host defense against Francisella novicida wild-type (WT) U112 and mutant strain XWK4. Comparing with U112, XWK4 infection induced robust cytokine production, ASC-dependent inflammasome activation, and pyroptosis. Both AIM2 and NLRP3 were involved and played independent roles in XWK4-induced inflammasome activation. Type II interferon was partially required for XWK4-triggered inflammasome activation, which was different from type I interferon dependency in U112-induced inflammasome activation. Distinct from F. novicida U112 and Acinetobacter baumannii infection, Asc–/– mice were more resistant than WT mice response to XWK4 infection by limiting bacterial burden in vivo. The excessive inflammasome activation triggered by XWK4 infection caused dramatical cell death and pathological damage. Our study offers novel insights into mechanisms of inflammasome activation in host defense and provides potential therapeutic approach against bacterial infections and inflammatory diseases.

scholarly journals PGC-1α mediates a metabolic host defense response in human airway epithelium during rhinovirus infections

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aubrey N. Michi ◽  
Bryan G. Yipp ◽  
Antoine Dufour ◽  
Fernando Lopes ◽  
David Proud
Keyword(s):  
Host Defense ◽  
Barrier Function ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Cellular Damage ◽  
Epithelial Barrier ◽  
Airway Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Function ◽  
Epithelial Damage

AbstractHuman rhinoviruses (HRV) are common cold viruses associated with exacerbations of lower airways diseases. Although viral induced epithelial damage mediates inflammation, the molecular mechanisms responsible for airway epithelial damage and dysfunction remain undefined. Using experimental HRV infection studies in highly differentiated human bronchial epithelial cells grown at air-liquid interface (ALI), we examine the links between viral host defense, cellular metabolism, and epithelial barrier function. We observe that early HRV-C15 infection induces a transitory barrier-protective metabolic state characterized by glycolysis that ultimately becomes exhausted as the infection progresses and leads to cellular damage. Pharmacological promotion of glycolysis induces ROS-dependent upregulation of the mitochondrial metabolic regulator, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), thereby restoring epithelial barrier function, improving viral defense, and attenuating disease pathology. Therefore, PGC-1α regulates a metabolic pathway essential to host defense that can be therapeutically targeted to rescue airway epithelial barrier dysfunction and potentially prevent severe respiratory complications or secondary bacterial infections.

scholarly journals Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1615
Author(s):  
Zhongwei Zhang ◽  
Yosuke Kurashima
Keyword(s):  
Mast Cells ◽  
Chronic Inflammation ◽  
Regulatory Function ◽  
Type I ◽  
Allergic Reactions ◽  
Novel Approach ◽  
Molecular Patterns ◽  
Regulatory Functions ◽  
Damage Associated Molecular Patterns ◽  
Two Sides

It is well known that mast cells (MCs) initiate type I allergic reactions and inflammation in a quick response to the various stimulants, including—but not limited to—allergens, pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs). MCs highly express receptors of these ligands and proteases (e.g., tryptase, chymase) and cytokines (TNF), and other granular components (e.g., histamine and serotonin) and aggravate the allergic reaction and inflammation. On the other hand, accumulated evidence has revealed that MCs also possess immune-regulatory functions, suppressing chronic inflammation and allergic reactions on some occasions. IL-2 and IL-10 released from MCs inhibit excessive immune responses. Recently, it has been revealed that allergen immunotherapy modulates the function of MCs from their allergic function to their regulatory function to suppress allergic reactions. This evidence suggests the possibility that manipulation of MCs functions will result in a novel approach to the treatment of various MCs-mediated diseases.

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