Mast Cell Content Research Articles

Mast cell accumulation precedes tissue fibrosis induced by intravenously administered amorphous silica nanoparticles

Despite the increasing use of amorphous silica nanoparticles (SNPs) in biomedical applications, their toxicity after intravenous administration remains a major concern. We investigated the effects of single 7 mg/kg intravenous infusions of 13 nm SNPs on hemodynamic parameters in rats. Hematological and biochemical parameters were assessed at 7, 30, and 60 d post treatment. Silicon content in the liver, lungs, heart, and kidney was analyzed, as well as tissue histology with special emphasis on mast cell (MC) content. SNP infusion had no effect on hemodynamics, nor did it alter hematological or biochemical parameters. SNP retention in the liver was conspicuous for up to 60 d. Among the other organs analyzed, silicon content was significantly increased only in the lung at 1-h post infusion. Despite the relatively low dose, SNP administration caused extensive liver remodeling, including the formation of multiple foreign body-type granulomas starting 7 d post treatment, and subsequent development of fibrosis. Histopathological changes in the liver were not preceded by hepatocyte necrosis. We found increased MC abundance in the liver, lungs, and heart starting on day 30 post treatment. MC recruitment in the liver preceded fibrosis, suggesting that MCs are involved in liver tissue remodeling elicited by intravenously administered SNPs.

Mast Cell Concentrations in Peripheral and Central Giant Cell Granulomas: Is there any Angiogenetic Role?

In the maxillofacial region, giant cell granulomas occur in 2 clinical forms, central and peripheral. Despite histopathological similarity between these 2 forms totally different clinical behaviors have been reported. The present study was undertaken to compare mast cell and vascular concentrations in these pathologic lesions. In this cross-sectional descriptive study, 20 pathological samples of central giant cell granuloma (CGCG) and 20 samples of peripheral giant cell granuloma (PGCG) were selected and examined through toluidine blue staining for mast cell assessment and immunohistochemical staining by VEGEF antibody for comparing the number of mast cells. T-test, chi-squared test and backward multivariate linear regression were used for statistical analysis using SPSS 20. Statistical significance was set at P<0.05. This study showed significantly greater VEGF expression and mast cell concentrations in CGCG compared to PGCG cases. Also there was a significant correlation between VEGF expression and the concentration of mast cells. No relation was found between age, sex and site of the lesion and concentration of mast cells or VEGF expression. It is feasible that higher concentrations of mast cells in CGCG versus PGCG samples might lead to more aggressive clinical behavior via vascular proliferation and angiogenesis. However, other biologic mechanisms should be considered in this situation.

Allergic lung inflammation promotes atherosclerosis in apolipoprotein E-deficient mice

Inflammation drives asthma and atherosclerosis. Clinical studies suggest that asthmatic patients have a high risk of atherosclerosis. Yet this hypothesis remains uncertain, given that Th2 imbalance causes asthma whereas Th1 immunity promotes atherosclerosis. In this study, chronic allergic lung inflammation (ALI) was induced in mice by ovalbumin sensitization and challenge. Acute ALI was induced in mice by ovalbumin and aluminum sensitization and ovalbumin challenge. Atherosclerosis was produced in apolipoprotein E-deficient (Apoe(-/-)) mice with a Western diet. When chronic ALI and atherosclerosis were produced simultaneously, ALI increased atherosclerotic lesion size, lesion inflammatory cell content, elastin fragmentation, smooth muscle cell (SMC) loss, lesion cell proliferation, and apoptosis. Production of acute ALI before atherogenesis did not affect lesion size, but increased atherosclerotic lesion CD4(+) T cells, lesion SMC loss, angiogenesis, and apoptosis. Production of acute ALI after atherogenesis also did not change atherosclerotic lesion area, but increased lesion elastin fragmentation, cell proliferation, and apoptosis. In mice with chronic ALI and diet-induced atherosclerosis, daily inhalation of a mast cell inhibitor or corticosteroid significantly reduced atherosclerotic lesion T-cell and mast cell contents, SMC loss, angiogenesis, and cell proliferation and apoptosis, although these drugs did not affect lesion area, compared with those that received vehicle treatment. In conclusion, both chronic and acute ALI promote atherogenesis or aortic lesion pathology, regardless whether ALI occurred before, after, or at the same time as atherogenesis. Antiasthmatic medication can efficiently mitigate atherosclerotic lesion pathology.

Therapeutic effect of ethyl acetate extract from Asparagus cochinchinensis on phthalic anhydride-induced skin inflammation.

Asparagus cochinchinensis has been used to treat various diseases including fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease, while IL-4 cytokine has been considered as key regulator on the skin homeostasis and the predisposition toward allergic skin inflammation. However, few studies have investigated its effects and IL-4 correlation on skin inflammation to date. To quantitatively evaluate the suppressive effects of ethyl acetate extracts of A. cochinchinensis (EaEAC) on phthalic anhydride (PA)-induced skin inflammation and investigate the role of IL-4 during their action mechanism, alterations in general phenotype biomarkers and luciferase-derived signals were measured in IL-4/Luc/CNS-1 transgenic (Tg) mice with PA-induced skin inflammation after treatment with EaEAC for 2 weeks. Key phenotype markers including lymph node weight, immunoglobulin E (IgE) concentration, epidermis thickness and number of infiltrated mast cells were significantly decreased in the PA+EaEAC treated group compared with the PA+Vehicle treated group. In addition, expression of IL-1β and TNF-α was also decreased in the PA+EaEAC cotreated group, compared to PA+Vehicle treated group. Furthermore, a significant decrease in the luciferase signal derived from IL-4 promoter was detected in the abdominal region, submandibular lymph node and mesenteric lymph node of the PA+EaEAC treated group, compared to PA+Vehicle treated group. Taken together, these results suggest that EaEAC treatment could successfully improve PA-induced skin inflammation of IL-4/Luc/CNS-1 Tg mice, and that IL-4 cytokine plays a key role in the therapeutic process of EaEAC.

Mast Cell Interaction with Neutrophils in Human Gastric Carcinomas: Ultrastructural Observations.

Aim. The role of mast cells in cell-cell immune interactions has received increasing attention, although their functional interaction with neutrophils still remains to be clarified in tumors. The aim of the present study was to investigate the association between mast cells and neutrophils in a series of gastric carcinomas (GC). Patients and Methods. 52 surgically resected GC specimens were routinely processed for both light and electron microscopy. Only cases showing both mast cells and neutrophils in the tumor stroma were considered in the analysis. Results. Only 9 GC (M : F = 5 : 4; age range: 50–82 years) showed both mast cells and neutrophils in the tumor stroma. At ultrathin sections, we identified heterotypic aggregation and intermingling of mast cells and neutrophils. Mast cells had mature phenotype and showed full complement of granules with homogeneous, scroll, particle, and mixed pattern. In addition, we found normal-appearing or early apoptosis showing neutrophils. Conclusion. Our histological findings showed the likely interaction between mast cells and neutrophils in GC. We hypothesize that the granular content of mast cells may be released in small quantity through a mechanism called “kiss-and-run fusion,” which is alternative to well-known massive anaphylactic or piecemeal degranulation.

Allergic Lung Inflammation Aggravates Angiotensin II-Induced Abdominal Aortic Aneurysms in Mice.

Asthma and abdominal aortic aneurysms (AAA) both involve inflammation. Patients with asthma have an increased risk of developing AAA or experiencing aortic rupture. This study tests the development of one disease on the progression of the other. Ovalbumin sensitization and challenge in mice led to the development of allergic lung inflammation (ALI). Subcutaneous infusion of angiotensin II into mice produced AAA. Simultaneous production of ALI in AAA mice doubled abdominal aortic diameter and increased macrophage and mast cell content, arterial media smooth muscle cell loss, cell proliferation, and angiogenesis in AAA lesions. ALI also increased plasma IgE, reduced plasma interleukin-5, and increased bronchioalveolar total inflammatory cell and eosinophil accumulation. Intraperitoneal administration of an anti-IgE antibody suppressed AAA lesion formation and reduced lesion inflammation, plasma IgE, and bronchioalveolar inflammation. Pre-establishment of ALI also increased AAA lesion size, lesion accumulation of macrophages and mast cells, media smooth muscle cell loss, and plasma IgE, reduced plasma interleukin-5, interleukin-13, and transforming growth factor-β, and increased bronchioalveolar inflammation. Consequent production of ALI also doubled lesion size of pre-established AAA and increased lesion mast cell and T-cell accumulation, media smooth muscle cell loss, lesion cell proliferation and apoptosis, plasma IgE, and bronchioalveolar inflammation. In periaortic CaCl2 injury-induced AAA in mice, production of ALI also increased AAA formation, lesion inflammation, plasma IgE, and bronchioalveolar inflammatory cell accumulation. This study suggests a pathological link between airway allergic disease and AAA. Production of one disease aggravates the progression of the other.

Mast cell, the peculiar member of the immune system: A homeostatic aspect.

The mast cell is a member of the immune system having a basic role in allergic (anaphylactic) reactions. However, it contains, synthesizes, stores and secretes lots of substances, which initiates other reactions or participates in them. These are in connection with the deterioration of tissue correlation, as malignant tumors, angiogenesis, wound healing, pregnancy and different pathological conditions. In addition - as other members of the immune system - mast cells can synthesize, store and secrete hormones characteristic to the endocrine glands and can transport them to the site of requirement (packed transport), or produce and employ them locally. The effect of mast cells is controversial and frequently dual, stimulatory or inhibitory to the same organ or process. This is likely due to the heterogeneity of the mast cells, in morphology and cell content alike and dependent on the actual condition of the targeted tissue. The cells are transported in an unmatured form by the blood circulation and are exposed to microenvironmental effects, which influence their maturation. Their enrichment around tumors suggested using them as targets for tumor therapy more than fifty years ago (by the author), however, this idea lives its renaissance now. The review discusses the facts and ideas critically.

Combination treatment for allergic conjunctivitis – Plant derived histidine decarboxylase inhibitor and H1 antihistaminic drug

Aim of present investigation was to study the effect of catechin and the combination of catechin and cetirizine in ovalbumin induced animal model of allergic conjunctivitis. Guinea pigs were divided into 5 groups: normal control, disease control, disease treated with catechin 100 mg/kg, disease treated with cetirizine 10 mg/kg, disease treated with combination of catechin and cetirizine, 50 mg/kg & 5 mg/kg respectively. Sensitization was carried out by intraperitoneal injection of ovalbumin for the period of 14 day. Simultaneously, catechin was administered orally for 14 days while, cetirizine was administered at the day of experiment. Determination of clinical scoring, mast cell and blood histamine content, histidine decarboxylase activity from stomach was carried out. Vascular permeability was measured by dye leakage after secondary challenge of allergen and conjunctival tissues were subjected for histopathological examinations. Treatment with catechin, cetirizine and combination showed significant (P < 0.05) decrease in clinical scoring and vascular permeability. While, catechin 100 mg/kg and catechin 50 mg/kg showed significant (P < 0.05) decrease in histamine content in mast and blood. The treatment also showed significant (P < 0.05) decrease in the histidine decarboxylase enzyme activity. However, cetirizine group did not show any difference in enzyme activity as well as histamine content. Histopathological examination also showed improvement in ulceration and decrease in edema and inflammation in all treatment groups. From the present study, we can conclude that catechin exhibits potent anti-allergic activity by histidine decarboxylase enzyme inhibition and combination shown significant anti-allergic activity at reduced dose by both enzyme inhibition as well as inhibition of histamine receptors.

Number Density of Mast Cells in the Primo Nodes of Rats

Mast cells (MCs) play a major role in allergic reactions. Surprisingly, the acupuncture points have a higher density of MCs compared with nonacupoints in the skin, which is consistent with the augmentation of the immune function by acupuncture treatment. We hypothesized that the primo vascular system (PVS), which was proposed as the anatomical structure of the acupuncture points and meridians, should have a high density of MCs. In order to test that hypothesis, we investigated the primo nodes isolated from the surfaces of internal organs, such as the liver, the small and the large intestines, and the bladder. The harvested primo nodes were stained with toluidine blue, and the MCs were easily recognized by their red–purple stains and their characteristic granules. The results showed a high density of MCs in the primo nodes and confirmed the hypothesis. The MCs were uniformly distributed in the nodes. The relative concentration of the MCs with respect to other cells was ∼15%. We divided the sizes of the primo nodes into three classes: large, medium, and small. The number density and the relative concentration of MCs did not show a size-dependence. The current work suggests that the PVS may participate in the immune response to allergic inflammation, which closely involves MCs.

Proton-Pump Inhibitor Treatment in Eosinophilic Esophagitis is Associated with Decreased Eosinophil Degranulation

Eosinophilic esophagitis (EoE) is an increasingly recognized disorder whose diagnosis is based on histologic demonstration of eosinophilic inflammation. We previously reported improvement of symptoms in children with EoE on long-term proton-pump inhibitor (PPI) monotherapy despite persistent eosinophilic inflammation. We sought to determine whether PPI monotherapy in children with EoE is associated with decreased eosinophil degranulation. Ten children with EoE had esophageal biopsies assessed for eosinophil, mast cell and Langerhans cell concentration and eosinophil degranulation at diagnosis and following PPI treatment. There was no significant difference in cell concentrations between initial and one-year follow-up. A significant decrease in number of free lying granules was observed at the one-year follow-up biopsies. Prolonged PPI therapy in EoE is associated with decreased eosinophil degranulation.

Modulation of extracellular ATP content of mast cells and DRG neurons by irradiation: studies on underlying mechanism of low-level-laser therapy.

Low-level-laser therapy (LLLT) is an effective complementary treatment, especially for anti-inflammation and wound healing in which dermis or mucus mast cells (MCs) are involved. In periphery, MCs crosstalk with neurons via purinergic signals and participate in various physiological and pathophysiological processes. Whether extracellular ATP, an important purine in purinergic signaling, of MCs and neurons could be modulated by irradiation remains unknown. In this study, effects of red-laser irradiation on extracellular ATP content of MCs and dorsal root ganglia (DRG) neurons were investigated and underlying mechanisms were explored in vitro. Our results show that irradiation led to elevation of extracellular ATP level in the human mast cell line HMC-1 in a dose-dependent manner, which was accompanied by elevation of intracellular ATP content, an indicator for ATP synthesis, together with [Ca2+]i elevation, a trigger signal for exocytotic ATP release. In contrast to MCs, irradiation attenuated the extracellular ATP content of neurons, which could be abolished by ARL 67156, a nonspecific ecto-ATPases inhibitor. Our results suggest that irradiation potentiates extracellular ATP of MCs by promoting ATP synthesis and release and attenuates extracellular ATP of neurons by upregulating ecto-ATPase activity. The opposite responses of these two cell types indicate complex mechanisms underlying LLLT.

Chymase mediates injury and mitochondrial damage in cardiomyocytes during acute ischemia/reperfusion in the dog.

Cardiac ischemia and reperfusion (I/R) injury occurs because the acute increase in oxidative/inflammatory stress during reperfusion culminates in the death of cardiomyocytes. Currently, there is no drug utilized clinically that attenuates I/R injury in patients. Previous studies have demonstrated degranulation of mast cell contents into the interstitium after I/R. Using a dog model of I/R, we tested the role of chymase, a mast cell protease, in cardiomyocyte injury using a specific oral chymase inhibitor (CI). 15 adult mongrel dogs had left anterior descending artery occlusion for 60 min and reperfusion for 100 minutes. 9 dogs received vehicle and 6 were pretreated with a specific CI. In vivo cardiac microdialysis demonstrated a 3-fold increase in interstitial fluid chymase activity in I/R region that was significantly decreased by CI. CI pretreatment significantly attenuated loss of laminin, focal adhesion complex disruption, and release of troponin I into the circulation. Microarray analysis identified an I/R induced 17-fold increase in nuclear receptor subfamily 4A1 (NR4A1) and significantly decreased by CI. NR4A1 normally resides in the nucleus but can induce cell death on migration to the cytoplasm. I/R caused significant increase in NR4A1 protein expression and cytoplasmic translocation, and mitochondrial degradation, which were decreased by CI. Immunohistochemistry also revealed a high concentration of chymase within cardiomyocytes after I/R. In vitro, chymase added to culture HL-1 cardiomyocytes entered the cytoplasm and nucleus in a dynamin-dependent fashion, and promoted cytoplasmic translocation of NR4A1 protein. shRNA knockdown of NR4A1 on pre-treatment of HL-1 cells with CI significantly decreased chymase-induced cell death and mitochondrial damage. These results suggest that the beneficial effects of an orally active CI during I/R are mediated in the cardiac interstitium as well as within the cardiomyocyte due to a heretofore-unrecognized chymase entry into cardiomyocytes.

Utility of Ki-67, CD10, CD34, p53, CD117, and Mast Cell Content in the Differential Diagnosis of Cellular Fibroadenomas and in the Classification of Phyllodes Tumors of the Breast

Adequate management of phyllodes tumors of the breast (PTB) remains a challenge because of the difficulty in correctly establishing preoperative diagnosis. The aim of this study was to evaluate the usefulness of Ki-67, CD10, CD34, p53, CD117, and of the number of mast cells in the differential diagnosis of benign PTB and cellular fibroadenomas (CFs) as well as in the grading of PTB. Fifty-one primary PTB and 14 CFs were examined by immunohistochemistry.When evaluating CD117 expression, higher epithelial expression was present in CF as well as an increased number of mast cells in benign PTB. Stromal expression of Ki-67, CD10, CD34, and p53 were relevant to PTB grading, of which the first 3 showed significance in the distinction of benign and borderline PTB, as well as between benign and malignant PTB. P53 was relevant only for the discrimination between benign and malign PTB. None of the markers showed significance in distinguishing between borderline and malign PTB.

Anaphylaxis in dogs and cats

To review and summarize current information regarding the pathophysiology and clinical manifestations associated with anaphylaxis in dogs and cats. The etiology, diagnosis, treatment, and prognosis is discussed. Anaphylaxis is a systemic, type I hypersensitivity reaction that often has fatal consequences. Many of the principal clinical manifestations involve organs where mast cell concentrations are highest: the skin, the lungs, and the gastrointestinal tract. Histamine and other deleterious inflammatory mediators promote vascular permeability and smooth muscle contraction; they are readily released from sensitized mast cells and basophils challenged with antigen. Anaphylaxis may be triggered by a variety of antigens including insect and reptile venom, a variety of drugs, vaccines, and food. Anaphylaxis is a clinical diagnosis made from a collection of signs and symptoms. It is most commonly based on pattern recognition. Differential diagnoses include severe asthma, pheocromocytoma, and mastocytosis. Epinephrine is considered the drug of choice for the treatment of anaphylaxis. It acts primarily as a vasopressor in improving hemodynamic recovery. Adjunctive treatments include fluid therapy, H1 and H2 antihistamines, corticosteroids, and bronchodilators; however, these do not substitute for epinephrine. Prognosis depends on the severity of the clinical signs. The clinical signs will vary among species and route of exposure. The most severe clinical reactions are associated when the antigen is administered parenterally.

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation

Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability.

Elemental Diet Induces Histologic Response in Adult Eosinophilic Esophagitis

Elemental diets have not been studied in adults with eosinophilic esophagitis (EoE). The goal of this trial was to assess the efficacy of an elemental diet in adults with EoE. A total of 18 adults with EoE were given an elemental diet for 4 weeks, or just 2 weeks if their response was complete. Symptoms and histologic findings, based on biweekly biopsies, were monitored. Six subjects were rebiopsied 2-7 days after resuming a normal diet. After therapy, esophageal tissue eosinophil content decreased from 54 to 10 per maximal high power field (P=0.0006). There was complete or nearly complete response (≤10 eosinophils) in 72% of subjects. Mast cell content, parabasal layer thickness, and endoscopic furrows and exudates also significantly decreased. Of the 29 qualified subjects, 11 (38%) failed to adhere to the diet. Several subjects had significant weight loss. Symptoms and endoscopic fixed strictures did not improve. After the subjects resumed a normal diet, the eosinophil content increased substantially in 3-7 days. While symptoms did not improve and dietary compliance was problematic, there was substantial histologic improvement after 4 weeks on the elemental diet. EoE in adults is substantially triggered by foods.

Immunohistochemical analysis of mast cell infiltrates and microvessel density in oral squamous cell carcinoma

The aim of the study was to evaluate mast cell concentration and microvessel density in perilesional and intralesional regions of oral squamous cell carcinoma (OSCC) and furthermore to assess the possible relationship between the above-mentioned parameters. Paraffin-embedded specimens from 47 cases of OSCC and 12 cases of normal mucosa were investigated immunohistochemically with anti-CD-31 antibody to stain microvessels and anti-tryptase antibody to visualize mast cells. The degree of vascularization and mast cell infiltration was measured with an image analysis system. The study revealed considerably increased microvessel density and mast cell abundance in intralesional and perilesional regions of OSCCs in comparison to normal mucosa. There was a significant positive correlation between microvessel density and mast cell concentration in both localizations of OSCCs (p < 0.02, p < 0.001, respectively), whereas a comparable correlation was not observed in normal mucosa. The obtained results suggest that mast cells play an important role in the regulation of angiogenesis in OSCC, although there are aspects of their activity of potential diagnostic and therapeutic significance which require further research.

Mast Cell Quantitation in Renal Biopsies as a Potential Marker for the Cumulative Burden of Tissue Injury

Background: Mast cells (MC) in kidney allograft biopsies have been associated with late biopsy scarring and poor outcomes. No specific quantitative studies or correlation with other histological parameters have been performed previously. Methods: Using the CD117 immunostain, MC were counted in the most inflamed area at 200 Magnification in 461 consecutive kidney allograft biopsies. The number of MC were correlated with the presence and severity of acute and chronic rejection features, including tubular, vascular and microvascular inflammation as well as glomerulitis, C4d positivity, transplant glomerulopathy, peritubular multilamellation, active transplant arteriopathy, high number of glomerular macrophages (>12) and the presence of interstitial fibrosis-tubular atrophy. Results: 275 (59.65%) KBx had 0-10 MC (Group 1), 102 (22.13%) had >10- 20 MC (Group 2) and 84 (18.22%) had >20 MC (Group C). No correlation was found between the number of MC and the presence or degree of T-cell mediated rejection or with parameters defining acute or chronic antibody mediated rejection. Significant correlation was found, however, with time post transplantation of the KBx: Group 1: 13.07 27.58; Group 2:31.27 33.57 and Group 3: 55.33 48.44 months post transplantation, p=.000. Typically MC were completely absent in biopsies performed within the first 10 days post transplantation. MC very rarely permeated tubular basement membranes (tubulitis) and were not found in glomeruli or vessels. Although increased concentration of MC was seen in inflamed scars, no statistical correlation was found between their number and the overall degree of interstitial fibrosis. Peritubular C4d+ correlated negatively with the number of MC as follows. No C4d+: 13.19 12.01 MC, Focal C4d+ (< 50%): 12.40 12.21 and diffuse C4d+ (>50%): 10.36 12.01 MD, p=.000. Conclusions: MC represent a somewhat unique cellular infiltrative component that does not correlate (or correlates negatively) with parameters of cellular or antibody mediated rejection. MC correlates strongly with the time post transplantation and could be potentially valuable as a surrogate marker for the cumulative burden of tissue injury that could supplement the notoriously unreliable (due to sampling variation) estimation of the degree of interstitial fibrosis/scarring.

Comparison between the concentration of mast cells and risk criteria of malignancy in intestinal adenomas

Intestinal adenomas are benign neoplasms that present a risk of malignancy associated with three independent characteristics: the polyp size, the histological architecture and the severity of epithelial dysplasia (or atypia). Current evidence suggests that mast cells (CM) contribute to the tumorigenesis of colorectal carcinomas. Objective: Compare the concentration of CM in intestinal adenomas and risk criteria for malignancy in these tumors (size, histological type and degree of cellular atypia). METHODS: We conducted a retrospective study with 102 anatomopathological reports of intestinal adenoma excision. We selected paraffin blocks with the central area of the tumor. The CM were stained with toluidine blue. RESULTS: In most cases (89.2%, n=91), the mast cells concentration (MC) was less than 6 CM/10 high power field (HPF) (p=0.0001). Most adenomas, regardless of their histological type, showed 0 CM/10 HPF (p=0.083). In most adenomas, regardless of their size, MC was 0 CM/10 HPF (p=0.665). Presence or absence of atypia was associated, in most cases, with MC of 0 CM/10 HPF (p=0.524). Conclusion: This study did not show association between the MC and histological type, size or presence of atypical cells in intestinal adenomas.

Early Macrophage and Mast Cell Responses in Diffuse Large B-Cell Lymphoma After Immunochemotherapy

Abstract 5206 Background:The prognostic impact of tumor microenvironment on the survival of lymphoma patients has recently been reported. However, early molecular and cellular responses to immunochemotherapy are unknown. Here, we have compared the tumor-associated macrophage (TAM) and mast cell (MC) contents in the lymphoma tissue in vivo before and after the first immunochemotherapy course in a small cohort of aggressive B-cell lymphoma patients. Patients and methods:The population of this pilot study consisted of seven diffuse large B-cell lymphoma (DLBCL) and three grade IIIB follicular lymphoma (FL) patients treated with rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen (immunochemotherapy). Paired tumor samples were collected before and a day after the first course of therapy, and evaluated immunohistochemically for CD68+, CD163+ macrophages and tryptase+ MCs. Freshly frozen lymphoma tissue containing enough material for paired mRNA analyses was available from 8 patients. Results:Comparing pre- and post-treatment tissue samples, an increase in the number of CD68+ TAMs was observed (p=0.023), whereas no variation in MC contents was found. If the patients were grouped according to response, i.e. remission (n=7) vs relapse (n=3), the most significant increase after therapy was observed in M2-type CD163+ TAM content (p=0.001). In the exon array analyses, the mRNA levels of both CD68 (p=0.052) and CD163 (p=0.023) genes increased after therapy. Conclusions:Our preliminary data suggest significant changes in macrophage content and their relative subsets in the lymphoma microenvironment after the first course of immunochemotherapy. Disclosures:No relevant conflicts of interest to declare.