Angiolipoma of the buccal mucosa: a possible role of mast cell-derived VEGF in its enhanced vascularity

A case of angiolipoma occurring in the buccal mucosa of a 69-year-old male is described. The patient had noticed a painless mass in his buccal mucosa for 2 years. The surgically removed tumor, measuring 9 mm in diameter, was mainly located in the submucosal layer with focal expansion into the muscle layer. Histologically, the tumor was well-demarcated and composed of proliferations of mature fat cells and fibrous connective tissue containing many small blood vessels, which were evenly distributed. There was diffuse infiltration of a large number of mast cells, which were immunopositive for vascular endothelial growth factor (VEGF) especially around blood vessels, suggesting that VEGF produced by mast cells in angiolipomas plays an important role in the vascular proliferation in this particular tumor.     

Analysis of mast cell subpopulations (MCT, MCTC) in cutaneous inflammation using novel enzyme-histochemical staining techniques

Abstract In order to gain insights into the dynamics of mast cell subpopulations in normal and diseased skin, a novel enzyme-histochemical double and triple staining method was employed that allowed the detection of metachromasia (toluidine blue) and the mast cell proteases tryp-tase and chymase within the same cell. Cryostat sections were used of skin biopsies from the following specimens: normal skin (N=4), psoriasis (N=13), atopic eczema (N=7), lichen planus (N=6), interferon α2a injection sites (N=l) of a leukemic infiltrate and corresponding normal skin of the same patient before and after treatment. (i) Equal numbers of tryptase-and chymase-positive mast cells (MCTC) were obtained in all normal and diseased specimens in papillary and reticular dermis, with threefold increases around appendages, (ii) Tryptase-positive mast cells (MCT) were absent in normal skin, but were markedly increased in a disease-specific pattern within the papillary dermis, the inflammatory infiltrate and around appendages, (iii) Marked increases of MCT were also noted at interferon injection sites within the leukemic infiltrate, but not in the normal skin of the same patient. These data suggest that disease-dependent mast cell dynamics involve only MCT in cutaneous inflammation and that MCT numbers are controlled by distinct, disease-specific local tissue factors.     

Anaphylactoid shock – a common cause of death in heroin addicts?

We measured mast-cell tryptase in postmortem blood from 22 heroin addicts dying suddenly after injection. In 32%, the concentration of tryptase was elevated (≥10 μg/1), and the mean value of tryptase was significantly different from a control group dying from known, nonimmunologic causes ( P <0.05). The increased tryptase concentrations indicate that death was preceded by systemic mast-cell degranulation. All victims of drug deaths had morphine in blood, most below 0.2 μg/ml. In 71% of the victims of drug-related deaths with tryptase values ≥10 μg/1, the intermediate degradation product, 6–monoacetyl-morphine, was not found in blood, whereas this was the case in only two victims with values below that cutoff point. This indicates that those with high tryptase concentrations survived longer than those with lower values. No correlation was found between the IgE levels and tryptase in either group, supporting the hypothesis that tryptase release was not mediated by an allergic reaction. The well-known property of opiates to stimulate unspecifically the liberation of histamine and other constituents of mast-cell granules offers one explanation of our observations. The results suggest that many heroin fatalities are caused by an anaphylactoid reaction.     

In vitro diagnosis of chronic nasal inflammation

BACKGROUND: Differential diagnosis of chronic nasal inflammation is insufficient when based solely on clinical examination and radiography of paranasal sinuses. Patients complain about more or less similar symptoms. Activation of mast cells and eosinophils is pivotal in nasal inflammation. OBJECTIVE: To compare tryptase and eosinophilic cationic protein (ECP) in nasal secretions in different forms of chronic nasal inflammation and to establish norm values. METHODS: The study included 1710 patients presenting with nasal complaints. Nasal secretions were gained by the cotton wool method and analysed for tryptase, as a marker of mast cell activation, and for ECP, as a marker of tissue eosinophilia and activation. Patients were grouped according to their diagnosis: chronic, non-allergic rhinosinusitis (sinusitis, n=194), non-allergic nasal polyposis (polyposis, n=138), non-allergic rhinitis with eosinophilia syndrome (NARES, n=198), isolated perennial allergic rhinitis (AR) (n=126), isolated seasonal AR (n=132), and patients allergic to both, seasonal and perennial allergens (n=193). Seven hundred and twenty-nine patients with nasal complaints due to a deviated septum and without any nasal inflammation served as controls. RESULTS: Nasal tryptase was highly significantly (P<0.001) elevated in polyposis, NARES, and in AR. ECP was highly significantly (P<0.001) elevated in all groups of patients suffering from chronic nasal inflammation. Based on our data and method we established norm values (95% confidence interval of mean value) for nasal tryptase in healthy adults, ranging from 12.0 to 18.7 ng/mL and for ECP ranging from 84.4 to 102.6 ng/mL. CONCLUSION: Mast cells and eosinophils are involved in non-allergic and allergic forms of chronic nasal inflammation. We established an in vitro assay for tryptase and ECP in nasal secretions and defined norm values based on our data and method. In vitro measurement of biological markers in nasal secretions provides important information for differential diagnosis and therapeutic strategies of chronic nasal inflammation.     

Effects on inflammation parameters of a double-blind,placebo controlled one-year course of SLIT in children monosensitized to mites

BACKGROUND: Clinical documentation about effects on local markers of inflammation of sublingual immunotherapy (SLIT) in children is still poor. METHODS: Twenty-four children (age range 4-16 years, average 8.5 years) monosensitized to house dust mites (HDMs) were randomized to receive active or placebo SLIT for this allergen according to a double-blind, placebo-controlled design. Before treatment and 10-12 months later the following parameters were checked: ECP and tryptase in sputum and nasal secretion, serum and nasal mite-specific IgE (sIgE), allergen-specific nasal challenge test (sNCT), nasal symptoms and tryptase after sNCT. RESULTS: Nasal tryptase and nasal IgE in basal conditions were unchanged in treated children but significantly increased in untreated children (P = 0.0156 and P = 0.0313, respectively). The threshold for sNCT was unchanged in both groups of children, but the symptom score after sNCT was unchanged in the placebo group and significantly decreased in the active group (P = 0.0084). The nasal tryptase after sNCT was unchanged in the active group and significantly increased in the placebo group (P = 0.0218). Intergroup comparison showed a significant difference in oral tryptase and nasal tryptase after sNCT in favour of the active group. CONCLUSIONS: These interim results after only 1 year of treatment show that SLIT in children monosensitized to HDMs is able to avoid the spontaneous increase in both nasal sIgE antibodies and in local allergic inflammation in basal conditions. These outcomes are confirmed and supported by the decrease of symptoms in the active group combined with the increase of nasal tryptase only in the control group in both cases after sNCT.     

Mast cell tryptase may modulate endothelial cell phenotype in healing myocardial infarcts

Mast cells and macrophages infiltrate healing myocardial infarcts and may play an important role in regulating fibrous tissue deposition and extracellular matrix remodelling. This study examined the time-course of macrophage and mast cell accumulation in healing infarcts and studied the histological characteristics and protease expression profile of mast cells in a canine model of experimental infarction. Although macrophages were more numerous than mast cells in infarct granulation tissue, macrophage density decreased during maturation of the scar, whereas mast cell numbers remained persistently elevated. During the inflammatory phase of infarction, newly recruited leucocytes infiltrated the injured myocardium and appeared to be clustered in close proximity to degranulating cardiac mast cells. During the proliferative phase of healing, mast cells had decreased granular content and were localized close to infarct neovessels. In contrast, macrophages showed no selective localization. Mast cells in healing canine infarcts were alcian blue/safranin-positive cells that expressed both tryptase and chymase. In order to explain the pro-inflammatory and angiogenic actions of tryptase--the major secretory protein of mast cells--its effects on endothelial chemokine expression were examined. Chemokines are chemotactic cytokines that play an important role in leucocyte trafficking and angiogenesis and are highly induced in infarcts. Tryptase, a proteinase-activated receptor (PAR)-2 agonist, induced endothelial expression of the angiogenic chemokines CCL2/MCP-1 and CXCL8/IL-8, but not the angiostatic chemokine CXCL10/IP-10. Endothelial PAR-2 stimulation with the agonist peptide SLIGKV induced a similar chemokine expression profile. Mast cell tryptase may exert its angiogenic effects in part through selective stimulation of angiogenic chemokines.     

Occupational asthma in a grain worker due to Lepidoglyphus destructor, assessed by bronchial provocation test and induced sputum

BACKGROUND: Occupational asthma (OA) can be a debilitating disease even when removal from the workplace is achieved. Today, the "gold standard" in the assessment of OA is the bronchial provocation test (BPT). Induced sputum is a non-invasive method of exploring airway inflammation which can provide additional information about such challenges and thus could be applied in OA diagnosis and monitoring. METHODS: We report the study carried out in a grain worker sensitized to Lepidoglyphus destructor (Ld), who suffered from mild asthma at the workplace. Skin prick test and specific serum IgE were measured. Ld-BPT was performed, and the changes in eosinophil rates, and ECP and tryptase levels in induced sputum were studied 30 min and 18 h after Ld-BPT. We also determined the changes in nonspecific bronchial hyperresponsiveness (NSBH), given as PD20 values. To assess the specificity of the changes, we also carried out sputum induction and methacholine challenge after barley-BPT. RESULTS: An isolated immediate response was obtained with Ld-BPT, while barley-BPT was negative. Induced sputum showed higher tryptase levels 30 min after Ld-BPT, and higher eosinophil and epithelial cell percentages and ECP levels 18 h after Ld-BPT. There was also a decrease in methacholine PD20 values after Ld-BPT. Those changes were not observed after barley-BPT. CONCLUSIONS: The study of eosinophilic and mast-cell markers in induced sputum provides additional knowledge about the inflammatory process occurring in the airways, suggesting that the study of induced sputum should be considered in the assessment of OA.     

乳腺肿瘤基质金属蛋白酶2表达与肥大细胞的关系

[目的]探讨乳腺肿瘤中基质金属蛋白酶2(matrix meta]]oproteinase2,MMP-2)表达及其与肥大细胞浸润的关系.[方法]采用甲苯胺蓝染色显示55例良恶性乳腺肿瘤组织的肥大细胞,免疫组化EnVision法检测肿瘤细胞MMP-2以及类胰蛋白酶(tryptase)的表达.[结果]乳腺癌间质成纤维细胞MMP-2的反应程度明显高于癌细胞.浸润性小叶癌和浸润性导管癌MMP-2的阳性率达86.7%,明显高于恶性程度较低的黏液腺癌和髓样癌(20.0%)以及乳腺的良性肿瘤(13.3%).局部有转移的乳腺癌组织中MMP-2的表达程度明显高于无转移组.乳腺肿瘤间质中肥大细胞的数量以及tryptase的表达量与MMP-2相似,但是与MMP-2的表达量并无明显的相关性.[结论]MMP-2的表达是乳腺癌一个预后指标,而肥大细胞的增多可能是肿瘤纤维间质形成的相伴现象.