Mast Cells In Lesions Research Articles

Mast cell infiltration in acute coronary syndromes: implications for plaque rupture

To define the role of mast cells in plaque destabilization. Inflammation is an essential feature of human coronary plaques. Macrophages and T lymphocytes are considered to contribute to destabilization of the plaques. The role of mast cells in this setting is less well studied. We therefore counted the mast cells in coronary atherectomy specimens from patients with chronic stable angina, unstable angina and severe unstable angina. Patients studied had chronic stable angina (group 1, n=11), "stabilized" unstable angina (group 2; Braunwald's class I and II, n=11) and "refractory" unstable angina (group 3; Braunwald's class III, n=7). Samples of culprit lesions (n=29) were obtained by directional atherectomy, snap-frozen and analyzed immunohistochemically. The numbers of mast cells and T lymphocytes per square millimeter squared were counted and the areas containing macrophages and smooth muscle cells were measured by computed planimetry. We found that the numbers of mast cells and T lymphocytes increased from group 1 through groups 2 to 3. Specimens from group 3 also contained the largest numbers of tumor necrosis factor alpha (TNF-alpha)-positive mast cells and of matrix metalloproteinase (MMP)-9 (92 kD gelatinase)-positive macrophages. Unstable coronary syndromes are associated with increased numbers of mast cells in culprit lesions. Activated mast cells secrete neutral proteases capable of degrading the extracellular matrix and TNF-alpha, capable of stimulating macrophages to synthesize MMP-9. Our observations suggest that mast cells, in addition to macrophages, contribute to matrix degradation and, hence, to progression of coronary syndromes.

Fascin and the differential diagnosis of childhood histiocytic lesions.

This is a descriptive screening of 46 examples of childhood histiocytic lesions and some of their look-alikes using a monoclonal antibody, p55, to fascin. Fascin, an actin-bundling protein, identifies dendritic cells in the blood and in tissues. Our aim was to test the diagnostic utility of the antibody in various lesions at different sites and to see whether the staining patterns give insight into the cell types involved. Fascin intensely stained the cells of juvenile xanthogranulomas (JXG), Rosai-Dorfman lesions, and soft tissue dendrocytomas. Normal Langerhans' cells and the cells of Langerhans' cell histiocytosis were unreactive. Their lack of fascin staining may be relevant to fascin being maturation as well as lineage related. Epithelioid and palisading granulomas were unstained, though an example of Kikuchi lymphadenitis had large numbers of dendritic-type cells that stained strongly. A reticulohistiocytoma of the skin was also unstained and look-alike lesions, Spitz nevi, and mast cell lesions did not stain. Two of three large-cell lymphomas (both CD30+) also had fascin reactivity. Even though fascin is not specific to dendritic cells, staining other cell types as well (false positive), and not entirely sensitive, dendritic cells such as tissue Langerhans' cells are unstained (false negative), there seems to be a consistency of staining in childhood histiocytic lesions. This may be of diagnostic use when read in the context of the tissue differential diagnosis. Whether fascin can serve as a marker for the dendritic cell lineage, or at least for some phases of dendritic cell lifecycle, is not answered by this survey.

Quantitative analysis of tryptase and chymase containing mast cells in benign and malignant breast lesions.

The aim of our work was to study the number and distribution of tryptase- and chymase-containing mast cells in benign and malignant breast lesions. Tryptase positivity reflects the total number of mast cells, whereas chymase is not present in all mast cells. Active forms of tryptase and chymase were demonstrated enzymo-histochemically in 30 benign and 98 malignant fresh frozen breast lesions, which were graded and analysed morphometrically and statistically. The exclusive presence of tryptase and chymase in mast cells was confirmed in 5 cases by a sequential double-staining method. In benign lesions, the number of mast cells exhibiting tryptase activity was similar to that of chymase-active mast cells. Malignant tumours, however, had 2 to 3 times more tryptase-containing than chymase-containing mast cells, while the number of mast cells with tryptase activity was significantly higher (p < 0.02) than in benign lesions. In malignant lesions, tryptase-containing mast cells were concentrated at the tumour edge, i.e., the "invasion zone," whereas chymase-containing mast cells were not increased in this area.

Quantitative analysis of tryptase and chymase containing mast cells in benign and malignant breast lesions

Quantitative analysis of tryptase and chymase containing mast cells in benign and malignant breast lesions

The role of mast cells in atherosclerosis.

Mast cells are characterized by numerous granules released extracellularly in response to stimuli, e.g. IgE and complement. These cells are believed to be crucial in the development of certain inflammatory or immune-mediated diseases, such as allergy and dermatitis, and it has recently been demonstrated that a large number of mast cells are present in atherosclerotic lesions. Atherosclerosis bears several similarities to chronic inflammation, characterized by T cell and monocyte infiltration, immunoglobulin-complement deposition, and lipid accumulation. The presence of mast cells in atherosclerotic lesions could be significant because they can release large amounts of chemotactic agents, inflammation activators, and granule remnants, and they may be responsible for mononuclear cell recruitment and smooth muscle cell proliferation. Furthermore, granule remnants nonspecifically bind to low-density lipoproteins, which can be phagocytosed by macrophages to form foam cells, a major cellular component of the early stage of atherosclerotic lesions. Thus, further elucidation of the role of mast cells in quantitative studies could enhance our understanding of the mechanism of atherogenesis, and may lead to new therapeutic strategies for atherosclerosis.

Alterations in mast cell proteinases and protease inhibitors in the progress of cutaneous herpes zoster infection.

The possible involvement of mast cell proteases in the cutaneous inflammation of herpes zoster was studied histochemically in ten patients. Mast cell tryptase and chymase bioactivities were demonstrated enzyme-histochemically. The localization of protease inhibitors as well as tryptase and chymase proteins in mast cells was established using a sequential double-staining method which first demonstrated bioactive tryptase or chymase, followed by immunohistochemical identification of these antigens. Biopsies were taken from involved vesicular and erythematous skin, as well as from normal healthy-looking skin. Tryptase-bioactive mast cells were significantly lower in number in the upper, but not in the deeper dermis of vesicular skin (68 +/- 37 cells/mm2, mean +/- SD) when compared with either healthy-looking (97 +/- 38) or erythematous skin (105 +/- 36) (t-test, P < 0.005). In contrast, chymase-bioactive mast cells were significantly reduced in number both in erythematous skin (44 +/- 20, P < 0.02) and even more so in vesicular skin (26 +/- 20, P < 0.0005) when compared with healthy-looking skin (64 +/- 27). The percentage of alpha 1-antitrypsin -immunoreactive and alpha 1-antichymotrypsin-immunoreactive mast cells in the upper dermis increased steadily from the values in healthy-looking skin (37.9 +/- 18.8 and 82.5 +/- 21.6 per cent) to those in erythematous (64.4 +/- 16.4 and 93.5 +/- 7.9 per cent) and vesicular skin (75.2 +/- 10.2 and 96.4 +/- 4 per cent). A novel finding was that cells showing tryptase immunoreactivity but no enzyme activity were found in two out of nine erythematous skin specimens and in four out of seven vesicular specimens. In healthy-looking skin, all cells with chymase immunoreactivity also displayed chymase bioactivity, but only 53.2 +/- 24.25 per cent of these mast cells in erythematous lesions and 44.4 +/- 15.9 per cent in vesicular lesions showed chymase bioactivity, suggesting inactivation of chymase by protease inhibitors. These results show prominent alterations in mast cell proteinases and protease inhibitors, indicating that these enzymes participate in the cutaneous inflammation due to herpes zoster.

Quantitative histochemical analysis of mast cells and sensory nerves in psoriatic skin.

To study the elements of neurogenic inflammation in psoriatic skin, morphological contacts were examined between mast cells and sensory nerves containing the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP) or vasoactive intestinal polypeptide (VIP). Because mast cells in psoriatic lesions appear in great numbers at the basement membrane (BM) zone, neuropeptide-mast cell contacts with the BM were also counted. A double stain for active mast cell tryptase and the neuropeptides was applied and the contacts were quantitated morphometrically. Sensory nerve-mast cell contacts were also studied three-dimensionally with a confocal laser scanning microscope. Increases in the contact values of SP and CGRP with mast cells, as well as with the BM, were obtained in developing (1-3 weeks) lesions when compared with their non-lesional controls. This increase reached statistical significance in mature lesions. In contrast, the corresponding contact values for VIP were decreased. By confocal microscopy, a close association between mast cells and sensory nerves was observed in the lesional dermis. Since tryptase is known to degrade CGRP but not SP, neurogenic stimuli, mainly via SP, can result in degranulation of mast cells, which release substances to enhance inflammation. At the BM zone in psoriatic lesions, the numerous mast cells loaded with tryptase can promote degradation of BM components and allow entry of various mediators to interact with keratinocytes.

Mitosis of mast cells in skin lesions of atopic dermatitis.

Mitoses of mast cells with cytoplasmic granules were observed in 6 out of 55 skin lesions of atopic dermatitis. It is thus likely that the local proliferation process of mast cells contributes to the increased number of mast cells in skin lesions of atopic dermatitis. Mitotic mast cells with cytoplasmic granules were also observed in 2 out of 8 dinitrochlorobenzene contact dermatitis lesions provoked in patients with atopic dermatitis. It is suggested that some mast cells in skin lesions of atopic dermatitis might be involved in the pathogenesis of type IV eczematous skin lesions of the disease.

Mast cells in oral erythema multiforme.

We compared the number of mast cells in erythema multiforme lesions, in clinically healthy mucosa between the EM attacks and in healthy mucosa from healthy volunteers. The mast cell count in patients with erythema multiforme was numerically higher than in healthy controls, but the differences were not statistically significant. In erythema multiforme lesions the mast cell count was low in the intensely inflamed superficial lamina propria, but high in normal appearing mucosa between the attacks suggesting local mast cell degranulation in the most intensely inflamed areas.

Hematologic Aspects of Mastocytosis: I: Bone Marrow Pathology in Adult and Pediatric Systemic Mast Cell Disease

The typical bone marrow lesions seen in adults with systemic mast cell disease (SMCD) are foci of spindle-shaped mast cells in a fibrotic matrix and are found in up to 90% of adults with SMCD. Lymphocytes and eosinophils frequently are admixed with the mast cells, forming the classic MEL lesion. The mast cell lesions can be found in perivascular, peritrabecular or intertrabecular locations and may on occasion completely replace intratrabecular regions of the marrow. In contrast, the mast cell lesions found in children with cutaneous mast cell disorders are uniformly small and subtle and are most frequently located perivascularly. Lymphocytes, eosinophils, and early myeloid elements may be associated with these lesions. Of perhaps greater specificity for SMCD is the finding of confluent clusters of mast cells on the marrow aspirates; such clusters are noted in up to 30% of patients with SMCD.

Urticaria pigmentosa. Systemic evaluation and successful treatment with topical steroids

Nine patients with adult-onset urticaria pigmentosa were studied for the incidence of extracutaneous mast cell involvement and the efficacy of potent topical corticosteroid therapy for cutaneous lesions. Seven of the nine patients had increased mast cells in the marrow biopsy specimens, and five patients had focal aggregates of mast cells. The bone scan was abnormal in one patient. Liver-spleen scans revealed a shift of colloid uptake from liver to spleen in four patients. No abnormal gastrointestinal tract roentgenograms were obtained. Urinary histamine metabolites correlated with nodular bone marrow involvement, but not with other parameters. Results of the psychoneurologic testing revealed significant deviation from the norm with a verbal memory deficit in all nine patients and abnormalities on the Minnesota Multiphasic Personality Inventory in four patients. All nine patients were treated with 0.05% betamethasone dipropionate ointment under occlusion over half of the body nightly for 6 weeks. Seven of nine patients treated responded with almost complete resolution of their lesions. Hypothalamic pituitary adrenal axis suppression was evaluated with intramuscular cosyntropin stimulation and metyrapone administration during treatment. Only two patients, both of whom used the medication improperly, developed transient abnormalities. Slow return of lesions was noted 6 months after completion of therapy. Remissions could be lengthened with single weekly applications of topical steroids. Systemic involvement is frequent in patients with cutaneous mast cell disease and it is best demonstrated by bone marrow biopsy. Mast cell lesions can be safely and effectively treated with topical steroids in motivated patients.

Urticaria Pigmentosa

† Nine patients with adult-onset urticaria pigmentosa were studied for the incidence of extracutaneous mast cell involvement and the efficacy of potent topical corticosteroid therapy for cutaneous lesions. Seven of the nine patients had increased mast cells in the marrow biopsy specimens, and five patients had focal aggregates of mast cells. The bone scan was abnormal in one patient. Liver-spleen scans revealed a shift of colloid uptake from liver to spleen in four patients. No abnormal gastrointestinal tract roentgenograms were obtained. Urinary histamine metabolites correlated with nodular bone marrow involvement, but not with other parameters. Results of the psychoneurologic testing revealed significant deviation from the norm with a verbal memory deficit in all nine patients and abnormalities on the Minnesota Multiphasic Personality Inventory in four patients. All nine patients were treated with 0.05% betamethasone dipropionate ointment under occlusion over half of the body nightly for 6 weeks. Seven of nine patients treated responded with almost complete resolution of their lesions. Hypothalamic pituitary adrenal axis suppression was evaluated with intramuscular cosyntropin stimulation and metyrapone administration during treatment. Only two patients, both of whom used the medication improperly, developed transient abnormalities. Slow return of lesions was noted 6 months after completion of therapy. Remissions could be lengthened with single weekly applications of topical steroids. Systemic involvement is frequent in patients with cutaneous mast cell disease and it is best demonstrated by bone marrow biopsy. Mast cell lesions can be safely and effectively treated with topical steroids in motivated patients. (<i>Arch Dermatol.</i>1991;127:191-196)

Mitoses of mast cells in atopic dermatitis lesions

Mitoses of mast cells in atopic dermatitis lesions

Mast cells in leprosy skin lesions.

The variability of mast cell density within and between leprosy skin lesions was examined as a basis for future studies, and whether the number of mast cells in the lesion was determined by local or systemic factors was evaluated. The mast cell density in the granuloma, skin appendages, and intervening dermis was assessed by counting mast cells in glycol methacylate sections stained with Giemsa stain and relating these counts to area measurements obtained by planimetry. In biopsy specimens taken from the edge of established lesions the density of mast cells within the granulomata was considerably higher than that in the intervening dermis and was comparable with that found in the appendages. No major differences in mast cell density were found between unaffected skin and the centre or edge of individual lesions. Mast cell densities in biopsy specimens from the edge of different lesions on the same patient were also similar, suggesting that the mast cell density within the granulomata is independent of the site of the lesion and is determined systemically.

Monoclonal Antibody MT1: A Marker for Langerhans Cell Histiocytosis

Langerhans cells and their pathologic counterparts can be identified in paraffin sections using immunohistochemical staining for S-100 protein. This procedure is useful in confirming a diagnosis of Langerhans cell histiocytosis (LCH). However, many other cell types are also positive for S-100 protein. Positive staining for CD1 (Leu 6) supports a diagnosis of LCH, but requires frozen tissue. A panel of antibodies would be desirable in confirming a diagnosis of LCH, particularly if these antibodies could be used on paraffin-embedded material. We studied the pattern of staining for commercially available monoclonal antibodies MT1, MT2, MB2, and LN1, which were originally marketed as lymphocyte markers, using paraffin-embedded tissue sections of cases of LCH. In all 20 cases pathologic Langerhans cells stained positively with MT1 only. Various other S-100 protein-positive lesions were also examined with MT1 and were consistently negative for MT1. Other cutaneous histiocytic and mast cell lesions were positive with MT1, but S-100 protein negative. Our results demonstrate that the monoclonal antibody MT1 serves as an additional marker for LCH and, together with S-100 protein, would make up a diagnostic panel of antibodies for LCH to be used on routine paraffin-embedded sections.

Hematopathology of the Bone Marrow in Pediatric Cutaneous Mastocytosis: A Study of 17 Patients

Sixteen bone marrow aspirates and 15 trephine core biopsies from 17 children with cutaneous mastocytosis, of which 15 exhibited urticaria pigmentosa and 2 exhibited diffuse cutaneous mastocytosis, were evaluated for the presence of bone marrow-associated pathologic conditions. Eight bone marrow aspirates from 8 children and 23 trephine core bone marrow biopsies from 16 children who had had evaluation for hematologic abnormalities not associated with cutaneous mastocytosis served as a control population. Eosinophilia was a prominent finding in bone marrows of 9 of 17 patients who had cutaneous mastocytosis. Increased mast cell numbers in bone marrow aspirates were observed in 5 children with cutaneous mastocytosis (5 of 16) and in 2 of the control children (2 of 8). Examination of the trephine core bone marrow biopsies obtained from patients with cutaneous mastocytosis demonstrated focal perivascular and paratrabecular aggregates consisting of mast cells, eosinophils, and early myeloid cells in 10 of 15 individuals. Similar lesions were observed in trephine core bone marrow biopsies of 3 of 16 control patients. The focal mast cell lesions characteristic of adult systemic mastocytosis were not observed. The authors conclude that cutaneous mastocytosis in the pediatric age group is rarely associated with definitive bone marrow findings suggestive of systemic mast cell disease and that this observation is consistent with previous reports that cutaneous mastocytosis in the majority of pediatric cases resolves by adulthood.

Heterogeneous distribution of mast cells in lichenified lesions of atopic dermatitis.

The aim of the present study was to determine whether the number of mast cells in lichenified lesions of atopic dermatitis (AD) have a relationship to familial background of atopic respiratory disease (ARD). We obtained biopsy specimens of lichenified lesions from 59 consecutive patients with AD. They included 35 AD patients who had a personal history of ARD, 9 AD patients without a personal history of ARD but with a family history of ARD, and 15 "pure" AD patients without a personal or a family history of ARD. From each biopsy specimen, 4 microns-thick paraffin-embedded sections and/or 1 micron-thick Epon-embedded sections were prepared, and stained with Giemsa's reagent. With both methods of preparation, the sections from AD patients with a personal history of ARD showed significantly greater mast cell number in lichenified lesions than the "pure" AD patients. It is suggested that the increase of mast cells often seen in AD lesions may be characteristic of a subgroup of AD patients who have a predisposition for ARD.

Histological evaluation of mast cells in rat gastric mucosal lesions induced by compound 48/80.

Repeated intraperitoneal administration of compound 48/80 to rats produced gastric lesions, a decrease in connective tissue mast cells (CTMCs) and an increase in gastric mucosal mast cells (MMCs). The ratio of MMC to CTMC was significantly correlated with lesion formation. A mast cell stabilizer, MAR-99 (50 mg/kg), prevented lesion formation and changes in the mast cells. Omeprazole (20 or 60 mg/kg) significantly reduced the gastric lesions, but mast cell changes persisted. Cimetidine (50 mg/kg) could not inhibit compound 48/80-induced lesions nor a decrease in CTMCs, but did prevent an increase in MMCs. These facts suggest that in compound 48/80-induced gastric lesions chemical mediators released from CTMCs might be trigger factors, while intraluminal gastric acid might be an aggravating factor. Furthermore, the increase in MMCs might be regulated by histamine released from the CTMCs via H2 receptors and have no causal relation to lesions formation.

Proteinase phenotypes and fixation properties of rat mast cells in parasitic lesions caused by Mesocestoides corti: selective and site-specific recruitment of mast cell subsets.

The distribution, fixation properties, and protease phenotypes of mast cells populating lesions caused by the metacestode stage of the cestode Mesocestoides corti in the rat were characterized. Intraperitoneal infection with M. corti induced severe granulomatous types of reactions around the pancreas and further lesions in the liver. These sites were infiltrated with mast cells which contained either rat mast cell protease I or II derived respectively from connective tissue (CTMC) or mucosal mast cells (MMC). A proportion of cells in pancreatic granulomas had staining and fixation properties identical to those of intestinal mucosal mast cells; others were typical connective tissue mast cells. Subcutaneous inoculation of parasites was associated with nodular dermal reactions, and all of the infiltrating mast cells had the fixation and staining properties of CTMC and contained RMCPI uniquely. Increased numbers of RMCPII-containing mast cells were present in the intestines of rats infected intraperitoneally. Significant quantities of RMCPII were present in homogenates of pancreatic granulomas and in livers of rats harbouring intraperitoneal infections but none was detected in skin. These findings suggest that mast cells of different phenotypes are selectively recruited to some, but not all, lesions.

Ultrastructural morphometric analysis of human mast cells in normal skin and pathological cutaneous lesions.

Electron micrographs of human mast cells in normal neonatal and adult skin and in cutaneous lesions of basal cell carcinoma (BCC), hemangioma and mastocytosis were assessed by morphometric analysis. Using this quantitative histologic approach, adult skin mast cells were found to be significantly larger (47.7 microns 2 +/- 2.4 SEM vs. 38.3 microns 2 +/- 1.8 SEM, p less than or equal to 0.001) and have larger granules (0.63 micron +/- .02 SEM vs. 0.53 micron +/- .02 SEM, p less than or equal to 0.001) than infant mast cells while both mast cell populations had comparable nuclear sizes (13.7 microns 2 +/- 0.9 SEM vs. 14.3 microns 2 +/- 0.8 SEM) and numbers of cytoplasmic granules (72 +/- 4.0 SEM vs. 66 +/- 4.0 SEM). Morphometric analysis of mast cell infiltrates in the adult skin lesions of BCC and hemangioma revealed that these cells were larger than neonatal mast cells but were similar to normal adult controls. Cutaneous mast cells from 2 mastocytosis patients, however, had significantly larger mean cell surface areas (78.0 microns 2 +/- 3.4 SEM and 70.6 microns 2 +/- 3.2 SEM, p less than or equal to 0.001), nuclear areas (20.8 microns 2 +/- 1.1 SEM and 21.3 microns 2 +/- 1.2 SEM p less than or equal to 0.001) and granule diameters (0.82 micron +/- 0.4 SEM and 0.83 micron +/- .03 SEM, p less than or equal to 0.001) when compared with mast cells in normal adult skin and in the other pathologic lesions. No difference in the total number of cytoplasmic granules was observed in the different mast cell populations.(ABSTRACT TRUNCATED AT 250 WORDS)