scholarly journals Molecular mechanism of mast cell–mediated innate defense against endothelin and snake venom sarafotoxin

2007 ◽  
Vol 204 (11) ◽  
pp. 2629-2639 ◽  
Author(s):  
Lars A. Schneider ◽  
Susan M. Schlenner ◽  
Thorsten B. Feyerabend ◽  
Markus Wunderlin ◽  
Hans-Reimer Rodewald
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Molecular Mechanism ◽  
Snake Venom ◽  
Single Amino Acid ◽  
Peptide Substrates ◽  
Innate Defense ◽  
Cell Enzyme ◽  
Peptide Family ◽  
Single Protease

Mast cells are protective against snake venom sarafotoxins that belong to the endothelin (ET) peptide family. The molecular mechanism underlying this recently recognized innate defense pathway is unknown, but secretory granule proteases have been invoked. To specifically disrupt a single protease function without affecting expression of other proteases, we have generated a mouse mutant selectively lacking mast cell carboxypeptidase A (Mc-cpa) activity. Using this mutant, we have now identified Mc-cpa as the essential protective mast cell enzyme. Mass spectrometry of peptide substrates after cleavage by normal or mutant mast cells showed that removal of a single amino acid, the C-terminal tryptophan, from ET and sarafotoxin by Mc-cpa is the principle molecular mechanism underlying this very rapid mast cell response. Mast cell proteases can also cleave ET and sarafotoxin internally, but such “nicking” is not protective because intramolecular disulfide bridges maintain peptide function. We conclude that mast cells attack ET and sarafotoxin exactly at the structure required for toxicity, and hence sarafotoxins could not “evade” Mc-cpa's substrate specificity without loss of toxicity.

scholarly journals Increased number of mast cells in epicardial adipose tissue of cardiac surgery patients with coronary artery disease

2020 ◽  
pp. 621-631
Author(s):  
K Rozsívalová ◽  
H Pierzynová ◽  
J Kratochvílová ◽  
M Lindner ◽  
M Lipš ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Mast Cell ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Mast Cells ◽  
Epicardial Adipose Tissue ◽  
Open Heart Surgery ◽  
Right Atrial ◽  
Innate Defense ◽  
Artery Disease

Chronic inflammation of adipose tissue is associated with the pathogenesis of cardiovascular diseases. Mast cells represent an important component of the innate defense system of the organism. In our work, we quantified mast cell number in epicardial adipose tissue (EAT), subcutaneous adipose tissue (SAT), and right atrial myocardium (RA) in patients undergoing open heart surgery (n=57). Bioptic samples of EAT (n=44), SAT (n=42) and RA (n=17) were fixed by 4 % paraformaldehyde and embedded into paraffin. An anti-mast cell tryptase antibody was used for immunohistochemical detection and quantification of mast cells. We also demonstrated immunohistochemically the expression of CD117 and chymase markers. In EAT of patients with coronary artery disease (CAD), higher incidence of mast cells has been found compared to patients without CAD (3.7±2.6 vs. 2.1±1.2 cells/mm(2)). In SAT and RA, there was no difference in the number of mast cells in CAD and non-CAD patients. Mast cells in SAT, EAT and RA expressed CD117 and chymase. An increased incidence of mast cells in EAT of CAD patients may indicate the specific role of these inflammatory cells in relation to EAT and coronary arteries affected by atherosclerosis.

scholarly journals AN ENZYME IN MAST CELLS WITH PROPERTIES LIKE CHYMOTRYPSIN

1959 ◽  
Vol 110 (3) ◽  
pp. 451-460 ◽  
Author(s):  
Earl P. Benditt ◽  
Margaret Arase
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Methyl Ester ◽  
Enzymatic Activity ◽  
Differential Centrifugation ◽  
Cell Enzyme ◽  
Sucrose Solutions ◽  
Naphthoic Acid ◽  
Activity Curve ◽  
Chymotrypsin A

Mast cells contain an enzyme which hydrolyzes 3-chloroacetoxy-2-naphthoic acid anilide. By using highly purified mast cells isolated by differential centrifugation in high density sucrose solutions we have been able to study this enzymatic activity in more detail. The enzyme has properties similar to those of chymotrypsin: Chymotrypsin will hydrolyze the histochemical substrate, and the chymotrypsin and mast cell activities with this substrate are similarly inhibited by diisopropylfluorophosphate. The mast cell enzyme is capable of hydrolyzing the N-acetyl esters of tryptophan, tyrosine, and phenylalanine, the relative rates of hydrolysis being similar to those seen with chymotrypsin. A characteristic trypsin substrate, p-toluenesulfonyl arginine methyl ester, is not acted upon by the mast cell enzyme or chymotrypsin. The pH activity curve of the new cell enzyme is similar to that of chymotrypsin as determined with N-acetyl-L-tryptophan ethyl ester as substrate.

scholarly journals Induction of Mast-Cell Accumulation by Promutoxin, an Arg-49 PhospholipaseA2

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Ji-Fu Wei ◽  
Xiao-Long Wei ◽  
Ya-Zhen Mo ◽  
Haiwei Yang ◽  
Shaoheng He
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Adhesion Molecules ◽  
Snake Venom ◽  
Platelet Activating Factor ◽  
Fold Increase ◽  
Inflammatory Cells ◽  
Cell Accumulation ◽  
Snake Venom Phospholipase ◽  
Main Component

Local inflammation is a prominent characteristic of snakebite wound, and snake-venom phospholipase A2s (PLA2s) are some of the main component that contribute to accumulation of inflammatory cells. However, the action of an R49 PLA2s, promutoxin fromProtobothrops mucrosquamatusvenom, on mast-cell accumulation has not been previously examined. Using a mouse peritoneal model, we found that promutoxin can induce approximately-6-fold increase in mast-cell accumulation, and the response lasts at least for 16 h. The promutoxin-induced mast cell accumulation was inhibited by cyproheptadine, terfenadine, and Ginkgolide B, indicating that histamine and platelet-activating factor (PAF) is likely to contribute to the mast-cells accumulation. Preinjection of antibodies against adhesion molecules ICAM-1, CD18, CD11a, and L-selectin showed that ICAM-1, and CD18, CD11a are key adhesion molecules of promutoxin-induced mast-cell accumulation. In conclusion, promutoxin can induce accumulation of mast cells, which may contribute to snake-venom wound.

scholarly journals Contribution of FcɛRI-associated vesicles to mast cell–macrophage communication following Francisella tularensis infection

2016 ◽  
Vol 22 (7) ◽  
pp. 567-574 ◽  
Author(s):  
Annette R Rodriguez ◽  
Jieh-Juen Yu ◽  
Christopher Navara ◽  
James P Chambers ◽  
M Neal Guentzel ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Francisella Tularensis ◽  
Direct Contact ◽  
Cellular Interactions ◽  
Microbial Infection ◽  
Innate Defense ◽  
Caspase 1 ◽  
Close Proximity ◽  
Pathogenic Microbes

Understanding innate immune intercellular communication following microbial infection remains a key biological issue. Using live cell imaging, we demonstrate that mast cells actively extend cellular projections to sample the macrophage periphery during Francisella tularensis LVS infection. Mast cell MHCIIhi expression was elevated from less than 1% to 13% during LVS infection. Direct contact during co-culture with macrophages further increased mast cell MHCIIhi expression to approximately 87%. Confocal analyses of the cellular perimeter revealed mast cell caspase-1 was localized in close proximity with FcɛRI in uninfected mast cells, and repositioned to clustered regions upon LVS infection. Importantly, mast cell FcɛRI-encompassed vesicles are transferred to macrophages by trogocytosis, and macrophage caspase-1 expression is further up-regulated upon direct contact with mast cells. Our study reveals direct cellular interactions between innate cells that may impact the function of caspase-1, a known sensor of microbial danger and requirement for innate defense against many pathogenic microbes including F. tularensis.

Cytochemical analysis of mast cell granules after poly-dl-lysine action

1978 ◽  
Vol 36 (2) ◽  
pp. 278-279
Author(s):  
R. Courtoy ◽  
L.J. Simar ◽  
J. Christophe
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Chemical Compounds ◽  
Cellular Membrane ◽  
Thin Sections ◽  
Organic Bases ◽  
Ferric Thiocyanate ◽  
Cytochemical Analysis ◽  
Mast Cell Granule ◽  
Amine Liberation

Several chemical compounds induce amine liberation from mast cells but do not necessarily provoque the granule expulsion. For example, poly-dl-lysine induces modifications of the cellular membrane permeability which promotes ion exchange at the level of mast cell granules. Few of them are expulsed but the majority remains in the cytoplasm and appears less dense to the electrons. A cytochemical analysis has been performed to determine the composition of these granules after the polylysine action.We have previously reported that it was possible to demonstrate polyanions on epon thin sections using a cetylpyridinium ferric thiocyanate method. Organic bases are selectively stained with cobalt thiocyanate and the sulfhydryle groups are characterized with a silver methenamine reaction. These techniques permit to reveal the mast cell granule constituents, i.e. heparin, biogenic amines and basic proteins.

Magnesium and sulfur in mast cell and basophil granules of lower vertebrates in relation with histamine

1992 ◽  
Vol 50 (2) ◽  
pp. 1596-1597
Author(s):  
Kenichi Takaya
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Mast Cell ◽  
Mast Cells ◽  
Tree Frog ◽  
X Ray ◽  
Transmission Electron ◽  
Scanning Transmission ◽  
Fresh Frozen ◽  
Ultrathin Sections

Mast cell and basophil granules of the vertebrate contain heparin or related sulfated proteoglycans. Histamine is also present in mammalian mast cells and basophils. However, no histamine is detected in mast cell granules of the amphibian or fish, while it is shown in those of reptiles and birds A quantitative x-ray microanalysis of mast cell granules of fresh frozen dried ultrathin sections of the tongue of Wistar rats and tree frogs disclosed high concentrations of sulfur in rat mast cell granules and those of sulfur and magnesium in the tree frog granules. Their concentrations in tree frog mast cell granules were closely correlated (r=0.94).Fresh frozen dried ultrathin sections and fresh air-dried prints of the tree frog tongue and spleen and young red-eared turtle (ca. 6 g) spleen and heart blood were examined by a quantitative energy-dispersive x-ray microanalysis (X-650, Kevex-7000) for the element constituents of the granules of mast cells and basophils. The specimens were observed by transmission electron microscopy (TEM) (80-200 kV) and followed by scanning transmission electron microscopy (STEM) under an analytical electron microscope (X-650) at an acceleration voltage of 40 kV and a specimen current of 0.2 nA. A spot analysis was performed in a STEM mode for 100 s at a specimen current of 2 nA on the mast cell and basophil granules and other areas of the cells. Histamine was examined by the o-phthalaldehyde method.

Mast cell-nerve fiber interaction: Ultrastructural studies

1990 ◽  
Vol 48 (3) ◽  
pp. 428-429
Author(s):  
E.Y. Chi ◽  
M.L. Su ◽  
Y.T. Tien ◽  
W.R. Henderson
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Substance P ◽  
Nerve Fiber ◽  
Sensory Nerves ◽  
Ultrastructural Studies ◽  
Morphological Studies ◽  
Granulocyte Infiltration ◽  
Intracutaneous Injection ◽  
Recent Attention

Recent attention has been directed to the interaction of the nerve and immune systems. The neuropeptide substance P, a tachykinnin which is a neurotransmitter in the central and peripheral nervous systems produces tissue swelling, augemntation of intersitial fibrin deposition and leukocyte infiltration after intracutaneous injection. There is a direct correlation reported between the extent of mast cell degranulation at the sites of injection and the tissue swelling or granulocyte infiltration. It has previously been demonstrated that antidromic electrical stimulation of sensory nerves induces degranulation of cutaneous mast cells, cutaneous vasodilation and augmented vascular permeability. Morphological studies have documented a close anatiomical association between mast cells and nonmyelinated nerves, that contain substance P and other neuropeptides. However, the presence of mast cells within nerve fasicles has not been previously examined ultrastructurally. In this study, we examined ultrastructurally the distribution of mast cells in the nerve fiber bundles located in the muscular connective tissue of rat tongues (n=20).

Ultrastructural evidence for mast cell-macrophage interrelationships in the dura mater of the rat: Infrequent mast cell-nerve associations

1990 ◽  
Vol 48 (3) ◽  
pp. 352-353
Author(s):  
Ruth V.W. Dimlich
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Dura Mater ◽  
Spatial Relationship ◽  
Potassium Phosphate ◽  
Plasma Extravasation ◽  
Close Spatial Relationship ◽  
Male Wistar Rats ◽  
Headache Pain ◽  
Relationship Of

Mast cells in the dura mater of the rat may play a role in cerebral pathologies including neurogenic inflammation (vasodilation; plasma extravasation) and headache pain . As has been suggested for other tissues, dural mast cells may exhibit a close spatial relationship to nerves. There has been no detailed ultrastructural description of mast cells in this tissue; therefore, the goals of this study were to provide this analysis and to determine the spatial relationship of mast cells to nerves and other components of the dura mater in the rat.Four adult anesthetized male Wistar rats (290-400 g) were fixed by perfusion through the heart with 2% glutaraldehyde and 2.8% paraformaldehyde in a potassium phosphate buffer (pH 7.4) for 30 min. The head of each rat was removed and stored in fixative for a minimum of 24 h at which time the dural coverings were removed and dissected into samples that included the middle meningeal vasculature. Samples were routinely processed and flat embedded in LX 112. Thick (1 um) sections from a minimum of 3 blocks per rat were stained with toluidine blue (0.5% aqueous).

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