scholarly journals Mast cells degranulation affects angiogenesis in the rat uterine cervix during pregnancy

Reproduction ◽  
2004 ◽  
Vol 127 (3) ◽  
pp. 379-387 ◽  
Author(s):  
J Varayoud ◽  
J G Ramos ◽  
V L Bosquiazzo ◽  
M Muñoz-de-Toro ◽  
E H Luque
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Blood Vessels ◽  
Uterine Cervix ◽  
Vascular System ◽  
Mast Cell Degranulation ◽  
Endothelial Cell Proliferation ◽  
Disodium Cromoglycate ◽  
Mast Cell Stabilizer ◽  
Vascular Area

During pregnancy, it is essential that sufficient nutrients are supplied by the vascular system to support the dramatic modifications of the rat uterine cervix. Angiogenesis refers to the growth of new blood vessels from pre-existing microcirculation and mast cells have been associated with this process. This study examined the modifications of the vascular compartment and the distribution of mast cells on cervical tissue during pregnancy. Using disodium cromoglycate as a mast cell stabilizer, we determined the effects of the mast cell degranulation on cervical angiogenesis. Mast cell distribution and their degranulation status were evaluated by immunohistochemistry. Endothelial cell proliferation was measured by bromodeoxyuridine incorporation. Vascular areas (absolute and relative) and maturation indices were assessed by quantitative immunohistochemistry of von Willebrand factor and α-smooth muscle actin respectively. Mast cells were predominantly observed during the first half of pregnancy in the perivascular zones. The values of bromodeoxyuridine incorporation, absolute vascular area and vascular maturation index exhibited a significant increase throughout pregnancy. All animals that received mast cell stabilizer showed more than 40% of non-degranulated mast cells. Treated rats exhibited a decrease in endothelial proliferation and in relative vascular area; in addition, a large proportion of mature blood vessels was observed, suggesting a diminished level of new vessel formation. The effects of the mast cell stabilizer were sustained beyond the end of treatment. This is the first report that brings evidence that mast cell degranulation could be a necessary process to contribute to the normal angiogenesis of the rat cervix during pregnancy. Further investigations are needed to elucidate the possible implications of abnormal vascular development of the uterine cervix on the physiological process of ripening and parturition.

Mediation of food protein-induced jejunal smooth muscle contraction in sensitized rats

1990 ◽  
Vol 259 (1) ◽  
pp. G6-G14 ◽  
Author(s):  
R. B. Scott ◽  
D. G. Gall ◽  
M. Maric
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Contractile Response ◽  
Specific Ige ◽  
Significant Loss ◽  
Tissue Type ◽  
Food Protein ◽  
Disodium Cromoglycate ◽  
Mast Cell Stabilizer

Alterations in myoelectric and motor activity are important features of food protein-induced intestinal anaphylaxis. To determine the mediator(s) involved, rats were sensitized by injection of egg albumin (10 micrograms ip), and controls were sham sensitized with saline. Fourteen days later the contractility of longitudinally oriented jejunal segments (mucosa intact) was examined in standard tissue baths in response to antigen (Ag) or other agents. Although control and sensitized tissues similarly contracted to stretch, bethanechol, histamine, or 5-hydroxytryptamine (5-HT), Ag contracted only sensitized segments. Contractile response 1) was specific to the sensitizing Ag, as bovine serum albumin did not induce contraction, and 2) could be passively transferred with serum containing specific IgE antibody. Mast cell degranulation after Ag challenge was suggested by a significant loss of granulated mast cells in sensitized compared with control rats challenged with Ag. Concanavalin A, which degranulates mucosal and connective tissue-type mast cells, and compound 48/80, which degranulates only connective tissue-type mast cells, produced a contractile response. Ag-induced contraction was significantly inhibited by the mucosal and connective tissue-type mast cell stabilizer doxantrazole (P less than 0.001) and the connective tissue mast cell stabilizer disodium cromoglycate (P less than 0.05). Diphenhydramine and cimetidine together blocked histamine-induced contraction but failed to affect Ag-induced contraction in sensitized tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Disodium cromoglycate stabilizes mast cell degranulation while reducing the number of hemoglobin-induced microvascular leaks in rat mesentery

2004 ◽  
Vol 286 (5) ◽  
pp. H1750-H1756 ◽  
Author(s):  
Maxwell I. Ginsburg ◽  
Ann L. Baldwin
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Blood Substitutes ◽  
Mast Cell Degranulation ◽  
Disodium Cromoglycate ◽  
Sprague Dawley ◽  
Plasma Albumin ◽  
Rat Mesentery ◽  
Sprague Dawley Rats ◽  
Infusion Experiment

Blood substitutes, such as diaspirin cross-linked Hb (DBBF-Hb), have been considered for use during blood transfusions. Unfortunately, bolus injection of modified Hb has been shown to rapidly increase the leakage of microvessels to plasma albumin. This effect may result from production of excess reactive oxygen species (ROS) and could be linked to the observed increase in degranulated mast cells (DMC). Disodium cromoglycate (cromolyn) stabilizes mast cells and therefore might minimize the venular permeability in the rat mesentery. In 10 anesthetized Sprague-Dawley rats, the mesenteric preparation was continuously suffused with cromolyn while the microvasculature was filled with DBBF-Hb solution (10 mg/ml) for 10 min. Six animals received cromolyn pretreatment [two intravascular injections over 30 min ( experiment A)] and four animals received pretreatment with 2% HEPES-buffered saline (HBS)-BSA ( experiment B). Two more animals were pretreated with HBS-BSA without DBBF-Hb infusion but with cromolyn suffusion ( experiment C). Another set of experiments was performed on five animals without cromolyn suffusion or any pretreatment but with DBBF-Hb infusion ( experiment D). All groups then received a 1-min perfusion of FITC-albumin, fixation for 60 min, and microscopic examination. Experiments A and B demonstrated a significant reduction in the number of venular leaks and DMC compared with experiment D, but not in the area of venular leaks. These results suggest mast cell degranulation is not a major contributor to microvascular leakage induced by DBBF-Hb.

Mast cells contribute to ischemia-reperfusion-induced granulocyte infiltration and intestinal dysfunction

1994 ◽  
Vol 267 (2) ◽  
pp. G316-G321 ◽  
Author(s):  
S. Kanwar ◽  
P. Kubes
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Ischemia Reperfusion ◽  
Mast Cell Degranulation ◽  
Mucosal Barrier ◽  
Mucosal Mast Cell ◽  
Epithelial Permeability ◽  
Barrier Dysfunction ◽  
Mast Cell Stabilizer ◽  
Granulocyte Infiltration

The objective of this study was to determine whether ischemia-reperfusion (I/R) of the small bowel activated mast cells and, if so, to determine whether this event contributed to granulocyte infiltration and mucosal barrier dysfunction. Autoperfused segments of the jejunum were exposed to 30 min of ischemia followed by 60 min of reperfusion. Epithelial permeability was assessed by the clearance of 51Cr-labeled EDTA from plasma to lumen. Plasma rat mast cell protease II (RMCP II) was measured and used as an index of mucosal mast cell degranulation, whereas myeloperoxidase (MPO) activity was used as an index of granulocyte infiltration. I/R caused a significant increase in plasma RMCP II levels, MPO activity, and epithelial permeability. The mucosal mast cell stabilizer doxantrazole prevented the I/R-induced increase in all three parameters. The connective tissue mast cell stabilizer ketotifen had no effect. To determine whether oxidants were involved in mast cell degranulation, some animals were pretreated with superoxide dismutase and catalase. This regimen completely abolished the I/R-induced rise in plasma RMCP II levels and attenuated mucosal MPO activity and epithelial permeability. Selective inhibitors of two mast cell-derived mediators, platelet-activating factor and histamine, did not attenuate the rise in epithelial permeability. These data suggest that oxidant-induced mucosal mast cell degranulation is a key event in the granulocyte infiltration and tissue dysfunction associated with reperfusion of the ischemic intestine.

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.

Cardiac mast cell-mediated activation of gelatinase and alteration of ventricular diastolic function

2002 ◽  
Vol 282 (6) ◽  
pp. H2152-H2158 ◽  
Author(s):  
Amanda L. Chancey ◽  
Gregory L. Brower ◽  
Joseph S. Janicki
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Marked Decrease ◽  
Volume Fraction ◽  
Normal Values ◽  
Mast Cell Degranulation ◽  
Ventricular Dilatation ◽  
Chemically Induced ◽  
Rat Hearts ◽  
Myocardial Collagen

Mast cells contain proteases capable of activating matrix metalloproteinases (MMPs). However, given the relatively low density of mast cells in the myocardium (i.e., 1.5–5.3 cells/mm2), it is unknown whether these enzymes are present in sufficient quantities in the normal heart to mediate MMP activation. Accordingly, this study sought to determine whether chemically induced degranulation of cardiac mast cells (with compound 48/80) would have an effect in isolated, blood-perfused, functioning rat hearts. Mast cell degranulation produced a 15% increase in histamine levels present in the coronary efflux, a significant increase in myocardial water (i.e., edema) relative to normal values (80.1 ± 3.4% vs. 77.4 ± 1.08%, P≤ 0.03), a substantial activation of MMP-2 (126% increase relative to controls, P ≤ 0.02), and a marked decrease in myocardial collagen volume fraction (0.46 ± 0.10% vs. 0.97 ± 0.33%, P ≤ 0.001). Furthermore, although an increase in ventricular stiffness was expected due to the extent of edema resulting from mast cell degranulation, modest ventricular dilatation was observed. These findings clearly demonstrate that the number of mast cells present in normal hearts is sufficient to mediate activation of MMPs and produce extracellular matrix degradation, thereby potentially causing subsequent ventricular dilatation.

scholarly journals Adenosine A2Areceptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation

2008 ◽  
Vol 295 (5) ◽  
pp. H1825-H1833 ◽  
Author(s):  
Tyler H. Rork ◽  
Kori L. Wallace ◽  
Dylan P. Kennedy ◽  
Melissa A. Marshall ◽  
Amy R. Lankford ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mast Cell Degranulation ◽  
Chimeric Mice ◽  
Cgs 21680 ◽  
Perfused Hearts

Mast cells are found in the heart and contribute to reperfusion injury following myocardial ischemia. Since the activation of A2Aadenosine receptors (A2AARs) inhibits reperfusion injury, we hypothesized that ATL146e (a selective A2AAR agonist) might protect hearts in part by reducing cardiac mast cell degranulation. Hearts were isolated from five groups of congenic mice: A2AAR+/+mice, A2AAR−/−mice, mast cell-deficient (KitW-sh/W-sh) mice, and chimeric mice prepared by transplanting bone marrow from A2AAR−/−or A2AAR+/+mice to radiation-ablated A2AAR+/+mice. Six weeks after bone marrow transplantation, cardiac mast cells were repopulated with >90% donor cells. In isolated, perfused hearts subjected to ischemia-reperfusion injury, ATL146e or CGS-21680 (100 nmol/l) decreased infarct size (IS; percent area at risk) from 38 ± 2% to 24 ± 2% and 22 ± 2% in ATL146e- and CGS-21680-treated hearts, respectively ( P < 0.05) and significantly reduced mast cell degranulation, measured as tryptase release into reperfusion buffer. These changes were absent in A2AAR−/−hearts and in hearts from chimeric mice with A2AAR−/−bone marrow. Vehicle-treated KitW-sh/W-shmice had lower IS (11 ± 3%) than WT mice, and ATL146e had no significant protective effect (16 ± 3%). These data suggest that in ex vivo, buffer-perfused hearts, mast cell degranulation contributes to ischemia-reperfusion injury. In addition, our data suggest that A2AAR activation is cardioprotective in the isolated heart, at least in part by attenuating resident mast cell degranulation.

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.

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