Arteriolar constriction in skeletal muscle during vascular stunning: role of mast cells

1997 ◽  
Vol 272 (5) ◽  
pp. H2154-H2163 ◽  
Author(s):  
M. W. Keller
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Vascular Reactivity ◽  
Striated Muscle ◽  
Mast Cell Degranulation ◽  
Response Curves ◽  
Maximal Diameter ◽  
Muscle Tissues ◽  
Stimulation Of

Striated muscle becomes stunned during reperfusion after sublethal ischemia. Resistance vessel tone and reactivity are altered in stunned muscle tissues. The hypothesis that adenosine-regulated mast cell degranulation occurs during reperfusion and leads to constriction of resistance arterioles was tested. The hamster cremaster muscle was subjected to 1 h of ischemia followed by reperfusion. Resistance arterioles constricted during reperfusion (74% of maximal diameter at baseline vs. 42% of maximal diameter after 30 min of reperfusion; P < 0.01). Mast cells degranulated in reperfusion concomitant with arteriolar constriction. Stimulation of mast cell degranulation in control animals with compound 48/80 or cold superfusate (21 degrees C) caused vasoconstriction that mimicked that seen in reperfusion. The mast cell stabilizer cromolyn blocked degranulation and constriction. If mast cell granules were depleted by applying compound 48/80 before inducing ischemia, then arterioles failed to constrict during reperfusion. Adenosine A3-antagonist BW-A1433 abolished constriction. These findings suggest that arterioles constrict in reperfusion due to adenosine-regulated mast cell degranulation. Vasodilation in response to sodium nitroprusside and acetylcholine was normal in stunned, constricted arterioles. However, the dose-response curves to adenosine were shifted to the left in arterioles constricted by either stunning, compound 48/80, exposure to cold superfusate, or cromolyn compared with control vessels. Depletion of granular components via stunning, compound 48/80, cold superfusate, or inhibition of secretion with cromolyn results in unopposed A1- or A2-mediated vasodilation in response to adenosine, whereas the dilatory effects of adenosine are blunted by simultaneous release of vasoconstrictors from mast cells in control animals. In summary, it was found that mast cell degranulation occurs during reperfusion and leads to constriction of resistance arterioles and altered vascular reactivity to adenosine. Adenosine is released in ischemia and stimulates mast cell degranulation via the A3 receptor located on mast cells during reperfusion.

scholarly journals Mast cell-mediated tumor-cell cytotoxicity. Role of the peroxidase system.

1981 ◽  
Vol 153 (3) ◽  
pp. 520-533 ◽  
Author(s):  
W R Henderson ◽  
E Y Chi ◽  
E C Jong ◽  
S J Klebanoff
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tumor Cells ◽  
Mast Cell Degranulation ◽  
Cell Secretion ◽  
51Cr Release ◽  
Tumoricidal Activity ◽  
Endogenous Peroxidase ◽  
Stimulation Of

Mast cells, when supplemented with H2O2 and iodide, are cytotoxic to mammalian tumor cells as determined by 51Cr release, and transmission and scanning electron microscopy. H2O2 at the concentration employed (10(-4) M) initiates mast cell degranulation, and mast cell granules (MCG), which contain a small amount of endogenous peroxidase activity, are toxic to tumor cells when combined with H2O2 and iodide. This toxicity is greatly increased by binding eosinophil peroxidase (EPO) to the MCG surface. Each component of the mast cell, MCG, or MCG-EPO system was required and toxicity was inhibited by the addition of the hemeprotein inhibitors azide or aminotriazole, which is compatible with a requirement for peroxidase in the cytotoxic reaction. A sequence of reactions is proposed in which mast cells, stimulated to release their granules by H2O2 generated by adjacent phagocytes, react with H2O2 and a halide to damage tumor cells. EPO release from eosinophils may contribute to this sequence of reactions, both by stimulation of H2O2-induced mast cell secretion and by combination with MCG to form a complex with augmented tumoricidal activity. These rections may play a role in the host defense against neoplasms.

scholarly journals Platelet and Erythrocyte Extravasation across Inflamed Corneal Venules Depend on CD18, Neutrophils and Mast Cell Degranulation

2021 ◽  
Vol 22 (14) ◽  
pp. 7360
Author(s):  
Angie De La Cruz ◽  
Aubrey Hargrave ◽  
Sri Magadi ◽  
Justin A. Courson ◽  
Paul T. Landry ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Types ◽  
Mast Cell Degranulation ◽  
Wild Type ◽  
Delayed Wound Healing ◽  
Corneal Epithelial ◽  
Corneal Abrasion ◽  
Low Levels ◽  
Endothelial Pores

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs passing through endothelial pores. In contrast, injured CD18hypo mice showed significantly less venule engorgement and markedly reduced platelet and RBC extravasation; mast cell degranulation was also reduced compared to WT mice. Corneal abrasion in mast cell-deficient (KitW-sh/W-sh) mice showed less venule engorgement, delayed PMN extravasation, reduced platelet and RBC extravasation and delayed wound healing compared to WT mice. Finally, antibody-induced depletion of circulating PMNs prior to corneal abrasion reduced mast cell degranulation, venule engorgement, and extravasation of PMNs, platelets, and RBCs. In summary, in the injured cornea, platelet and RBC extravasation depends on CD18, PMNs, and mast cell degranulation.

Comparative analysis of the role of mast cells in murine asthma models using Kit‐sufficient mast cell‐deficient animals

Allergy ◽  
2021 ◽  
Author(s):  
Lea Pohlmeier ◽  
Sanchaita Sriwal Sonar ◽  
Hans‐Reimer Rodewald ◽  
Manfred Kopf ◽  
Luigi Tortola
Keyword(s):  
Mast Cell ◽  
Comparative Analysis ◽  
Mast Cells

Mast cell heterogeneity

1984 ◽  
Vol 62 (6) ◽  
pp. 734-737 ◽  
Author(s):  
F. Shanahan ◽  
J. A. Denburg ◽  
J. Bienenstock ◽  
A. D. Befus
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Regulatory Peptides ◽  
Cell Heterogeneity ◽  
Cell Secretion ◽  
Biochemical Basis ◽  
Mucosal Mast Cells ◽  
Mast Cell Heterogeneity

Increasing evidence for the existence of inter- and intra-species mast cell heterogeneity has expanded the potential biological role of this cell. Early studies suggesting that mast cells at mucosal sites differ morphologically and histochemically from connective tissue mast cells have been confirmed using isolated intestinal mucosal mast cells in the rat and more recently in man. These studies also established that mucosal mast cells are functionally distinct from connective tissue mast cells. Thus, mucosal and connective tissue mast cells differ in their responsiveness to a variety of mast cell secretagogues and antiallergic agents. Speculation about the therapeutic use of antiallergic drugs in disorders involving intestinal mast cells cannot, therefore, be based on extrapolation from studies of their effects on mast cells from other sites. Regulatory mechanisms for mast cell secretion may also be heterogeneous since mucosal mast cells differ from connective tissue mast cells in their response to a variety of physiologically occurring regulatory peptides. The development of techniques to purify isolated mast cell sub-populations will facilitate future analysis of the biochemical basis of the functional heterogeneity of mast cells.

scholarly journals Mast cell activation is not required for induction of airway hyperresponsiveness by ozone in mice

1999 ◽  
Vol 86 (1) ◽  
pp. 202-210 ◽  
Author(s):  
N. Noviski ◽  
J. P. Brewer ◽  
W. A. Skornik ◽  
S. J. Galli ◽  
J. M. Drazen ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Airway Hyperresponsiveness ◽  
Essential Role ◽  
Cell Activation ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Polymorphonuclear Cell ◽  
Pulmonary Parenchyma

Exposure to ambient ozone (O3) is associated with increased exacerbations of asthma. We sought to determine whether mast cell degranulation is induced by in vivo exposure to O3in mice and whether mast cells play an essential role in the development of pulmonary pathophysiological alterations induced by O3. For this we exposed mast cell-deficient WBB6F1- kitW/ kitW-v( kitW/ kitW-v) mice and the congenic normal WBB6F1(+/+) mice to air or to 1 or 3 parts/million O3for 4 h and studied them at different intervals from 4 to 72 h later. We found evidence of O3-induced cutaneous, as well as bronchial, mast cell degranulation. Polymorphonuclear cell influx into the pulmonary parenchyma was observed after exposure to 1 part/milllion O3only in mice that possessed mast cells. Airway hyperresponsiveness to intravenous methacholine measured in vivo under pentobarbital anesthesia was observed in both kitW/ kitW-vand +/+ mice after exposure to O3. Thus, although mast cells are activated in vivo by O3and participate in O3-induced polymorphonuclear cell infiltration into the pulmonary parenchyma, they do not participate detectably in the development of O3-induced airway hyperresponsiveness in mice.

Mass cells contribute to O3-induced epithelial damage and proliferation in nasal and bronchial airways of mice

1996 ◽  
Vol 80 (4) ◽  
pp. 1322-1330 ◽  
Author(s):  
M. Longphre ◽  
L. Y. Zhang ◽  
J. R. Harkema ◽  
S. R. Kleeberger
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Dna Synthesis ◽  
Measured Parameter ◽  
Epithelial Injury ◽  
Epithelial Damage ◽  
Proinflammatory Mediators ◽  
Cell Counts ◽  
Air Control

Ozone (O3) exposure produces inflammation in the airways of humans and animal models. However, the mechanism by which O3 affects these changes is uncertain. Mast cells are strategically located below the epithelium of the airways and are capable of releasing a number of proinflammatory mediators. We tested the hypothesis that mast cells contribute to inflammation, epithelial sloughing, and epithelial proliferation in the nasal and terminal bronchiolar murine airways after O3 exposure. Mast cell-sufficient (+/+), mast cell-deficient (W/Wv), and mast cell-repleted [bone marrow-transplanted (BMT) W/Wv] mice were exposed to 2 ppm O3 or filtered air for 3 h. Nasal and bronchoalveolar lavage fluids were collected 6 and 24 h after exposure. Differential cell counts and protein content of the lavage fluids were used as indicators of inflammation and permeability changes in the airways. O3-induced epithelial injury was assessed by light microscopy, and O3-induced DNA synthesis in airway epithelium was estimated by using a 5-bromo-2′-deoxyuridine-labeling index in the nasal and terminal bronchiolar epithelia. Relative to air control mice, O3 caused significant increases in inflammation, epithelial injury, and epithelial DNA synthesis in +/+ mice. There was no significant effect of O3 exposure on any measured parameter in the W/Wv mice. To further assess the role of mast cells in O3-induced epithelial damage, mast cells were restored in W/Wv mice by BMT from +/+ congeners. Relative to sham-transplanted W/Wv mice, O3 caused significant increases in epithelial damage and DNA synthesis as well as inflammatory indicators in BMT W/Wv mice. These observations are consistent with the hypothesis that mast cells significantly modulate the inflammatory and proliferative responses of the murine airways to O3.

The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E2

2018 ◽  
Vol 11 (556) ◽  
pp. eaao4354 ◽  
Author(s):  
Ivana Halova ◽  
Monika Bambouskova ◽  
Lubica Draberova ◽  
Viktor Bugajev ◽  
Petr Draber
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
And Function ◽  
Cell Chemotaxis

Chemotaxis of mast cells is one of the crucial steps in their development and function. Non–T cell activation linker (NTAL) is a transmembrane adaptor protein that inhibits the activation of mast cells and B cells in a phosphorylation-dependent manner. Here, we studied the role of NTAL in the migration of mouse mast cells stimulated by prostaglandin E2 (PGE2). Although PGE2 does not induce the tyrosine phosphorylation of NTAL, unlike IgE immune complex antigens, we found that loss of NTAL increased the chemotaxis of mast cells toward PGE2. Stimulation of mast cells that lacked NTAL with PGE2 enhanced the phosphorylation of AKT and the production of phosphatidylinositol 3,4,5-trisphosphate. In resting NTAL-deficient mast cells, phosphorylation of an inhibitory threonine in ERM family proteins accompanied increased activation of β1-containing integrins, which are features often associated with increased invasiveness in tumors. Rescue experiments indicated that only full-length, wild-type NTAL restored the chemotaxis of NTAL-deficient cells toward PGE2. Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE2, which may act through the RHOA/ERM/β1-integrin and PI3K/AKT axes.

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