Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated and characterized the human cardiac mast cell (CMC) and compared this novel mast cell (MC type with MC obtained from uterus, skin, and lung. Heart tissue was obtained from 14 patients with cardiomyopathy (CMP, heart transplantation). CMC were isolated by enzymatic digestion using collagenase, pronase-E, hyaluronidase, and DNAse. Substantial amounts of CMC (0.5% to 1.5% of isolated cells) were found in the atrial appendages but not in ventricular digests or other sites of the heart (< 0.1%). In situ staining of atrial tissue revealed the presence of CMC in the myocardium (2.16 +/- 0.7 MC/mm2), endocardium (2.24 +/- 0.9 MC/mm2), and epicardium. As assessed by combined toluidine blue/immunofluorescence staining with monoclonal antibodies (MoAbs), isolated CMC expressed surface IgE, the receptor for stem cell factor (c-kit receptor/CD117), the p24 antigen (CD9), the Pgp-1 homing receptor (CD44), the pan leukocyte antigen (CD45), and the ICAM-1 antigen (CD54). CMC were not recognized by MoAbs to lymphocyte function associated antigen 2 (LFA-2; CD2), T-cell receptor (TcR; CD3), T4 antigen (CD4), LFA-1 alpha-chain (CD11a), C3biR alpha-chain (CD11b), CR4 alpha-chain (CD11c), LPS-R related Ag (CD14), 3-FAL/x-hapten (CD15), Fc gamma RIII (CD16), lactosylceramid (CDw17), the B-cell antigen CD19, or CR1 (CD35). In situ expression of leukocyte antigens on CMC was demonstrable by indirect immunoperoxidase staining technique and double-labeling immunohistochemistry. Almost all CMC (90%) reacted with MoAbs against tryptase and chymase and thus were MCTC. Cardiac mast cells were also stained by the heparin-binding dye Berberine sulfate and expressed measurable amounts of histamine (4.6 +/- 1.4 pg per cell). Cross linking of either IgE receptor or SCF receptor (c-kit) on CMC resulted in histamine secretion (non-specific release: < 6% of total histamine, alpha IgE induced: 12% to 52%; SCF-induced release: 9% to 18%), whereas neither substance P (a skin MC agonist) nor the basophil agonist FMLP showed an effect on CMC. Together, the CMC is an MCTC primarily located in the appendage of the atrium. This novel type of MC exhibits surface membrane antigen and functional properties similar to those of lung and uterus MC.
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PMID:The human cardiac mast cell: localization, isolation, phenotype, and functional characterization. 752 50

It has been proposed that a primary detector mechanism for tissue infection or injury may be the mast cell that releases agents that recruit leukocytes to the appropriate site at risk. The objective of this study was to evaluate the early mechanisms involved in mast cell-induced leukocyte recruitment. We used intravital microscopy to visualize leukocyte-rolling flux and adhesion in single 25 to 40 microns venules in mesenteric preparations that were treated with the mast cell-degranulating agent, compound 48/80 (CMP 48/80). Superfusion of the rat mesentery with CMP 48/80 caused a dose-dependent rise in the number of rolling and adherent cells, events significantly reduced by: 1) mast cell stabilizers, ketotifen, or cromolyn, and 2) chronic treatment with CMP 48/80 to deplete mast cell constituents. The increase in leukocyte flux associated with CMP 48/80 was blocked by diphenhydramine (H1-receptor antagonist) and an anti-P-selectin Ab (PB1.3), but not by the 5-lipoxygenase inhibitor, MK 886. The reduction in the flux of rolling leukocytes translated into fewer adherent leukocytes with diphenhydramine or PB1.3. The CMP 48/80-induced rise in leukocyte adhesion, but not leukocyte flux, was reduced by the platelet-activating factor (PAF)-receptor antagonist (WEB 2086) and an anti-CD18 Ab (CL26). MK 886 did not prevent the increased leukocyte adhesion. In vitro data revealed that mast cell-derived PAF induced essentially all of the leukocyte adhesion to endothelium or protein-coated plastic. These data suggest that mast cell degranulation induces P-selectin-dependent leukocyte rolling and CD18-dependent leukocyte adhesion via histamine and PAF, respectively.
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PMID:Mechanisms underlying acute mast cell-induced leukocyte rolling and adhesion in vivo. 781 84

The major objective of this study was to systematically elucidate the mechanisms underlying microvascular permeability in rat mesenteric venules after the activation of perivascular mast cells. Intravital microscopy was used to assess polymorphonuclear leukocyte (PMN) infiltration and microvascular permeability alterations in single 25- to 40-micron diameter venules. Ruthenium red was used to detect mast cell activation on-line. Exposure of mast cells to compound 48/80 (CMP 48/80) caused a rapid mast cell activation and increase in microvascular permeability (within 15 min) that was maintained for the duration of the experiment. CMP 48/80 also increased PMN adhesion to the microvascular endothelium. Anti-PMN serum, as well as various antiadhesion therapies, including CL26 (anti-CD18 antibody) and fucoidan (selectin-immunoneutralizing carbohydrate), revealed that the early microvascular permeability was PMN independent. However, these regimens significantly reduced plasma protein leakage out of venules between 30 and 60 min. Methysergide (serotonin receptor antagonist), but not diphenhydramine (histamine receptor antagonist), inhibited the early PMN-independent microvascular permeability. Finally, a platelet-activating factor (PAF)-receptor antagonist did not affect the early phase of microvascular permeability but reversed the later phase, consistent with PAF's role as a proadhesive molecule for PMN during mast cell activation. These data demonstrate that, within the first hour of mast cell activation, a biphasic PMN-independent and -dependent response in microvascular permeability is observed. The data also raise the possibility that histamine's physiological role in this model may be unrelated to alterations in microvascular permeability.
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PMID:Rapid mast cell activation causes leukocyte-dependent and -independent permeability alterations. 899 3

Inflammation consequent to muscle damage is characterized by an accumulation of leukocytes. Our aim in this study was to determine whether mast cells can modulate inflammation-induced leukocyte trafficking. One approach consisted of giving rats a mast cell-degranulating agent, CMP 48/80, prior to a protocol of lengthening contractions inducing inflammation without neutrophil accumulation; in parallel, other rats were given the mast cell-stabilizing agent, cromolyn, prior to injecting muscle with bupivacaine, which induces neutrophil accumulation. Damage was evaluated through measurement of contractile force and inflammation using histochemical and immunohistochemical methods. Stimulation with CMP 48/80 increased the proportion of degranulated mast cells significantly and neutrophil accumulation occurred with lengthening contractions. With bupivacaine, accumulation of neutrophils decreased by 70% when degranulation was inhibited. These results indicate that mast cells are important in the process governing leukocyte trafficking in skeletal muscle trauma and that targeting their inhibition could be an attractive alternative for control of inflammation.
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PMID:Inflammation-induced leukocyte accumulation in injured skeletal muscle: role of mast cells. 1850 8