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Gene expression profiling of human mast cell subtypes: an in silico study.

BACKGROUND: Human mast cells (MCs) were classified into at least two subtypes, i.e., tryptase- and chymase-positive MCs (MC(TC)) and tryptase-only-positive MCs (MC(T)). However, differences in global molecular expression between these subtypes are unknown. METHODS: We analyzed public microarray data of MC subtypes derived from various tissues and those of peripheral blood granulocytes by using hierarchical clustering methods to understand the global gene expression profiles. RESULTS: All the transcripts subjected to this clustering analysis were classified into two large clusters, i.e., MC-preferential or granulocyte-preferential. In the original works, MCs from tonsil, lung and skin had been cultured for more than several weeks to obtain highly viable and pure cell populations, and these MCs retained their typical profiles such as intensities of chymase protein expression. Most of the transcripts were commonly expressed by these MC subtypes. However, tonsil-derived MCs and skin-derived MCs but not lung-derived MCs expressed high levels of chymase (CMA1) as expected for the properties of MC(TC) and MC(T). These CMA1-high MCs and CMA1-low MCs respectively expressed distinct sets of transcripts as small gene clusters as well as CMA-1 even after being cultured in the absence of a tissue environment. CONCLUSIONS: The MC lineage seems to be far from the granulocyte lineages including basophils. CMA1-high MCs (MC(TC)) and CMA1-low MCs (MC(T)) can be regarded as differentiated MC subtypes. As such, importance of data analysis studies will be increasing along with the accumulation of global molecular data in the public database.

Cells, Cultured↗

Mast cells in cutaneous allergic vasculitis: a case report.

BACKGROUND: The mechanism of cutaneous allergic vasculitis still remains unclear, and to the best of our knowledge, no case has been reported in the literature in which the number of mast cells was examined. METHODS: A 33-year-old woman, with a past history of allergic rhinitis due to Japanese cedar and Phleum pratense (timothy), presented with a chief complaint of palpable papules on both lower legs in December 2002. On blood examination, peripheral blood eosinophilia was present, but all other examinations for immunologic diseases were negative, including specific IgE. We suspected cutaneous allergic vasculitis and performed skin biopsy. RESULTS: In December 2002, histological examination of biopsy specimens of the skin lesions showed leukocytoclastic vasculitis. The diagnosis of cutaneous allergic vasculitis was made based on the clinical symptoms and the pathological findings of biopsy specimens. Immunohistochemical staining for human mast cell tryptase using monoclonal antibody against human mast cell tryptase showed an accumulation of mast cells. Treatment with oral corticosteroid resulted in the disappearance of clinical symptoms, and the steroid tapered. A second skin biopsy was performed in June 2005 after informed consent was obtained. Histological examination showed no findings of leukocytoclastic vasculitis, and the number of mast cells had decreased. She has been well without treatment. CONCLUSIONS: Mast cells may increase in the skin lesion of cutaneous allergic vasculitis.

Adult↗

A pediatric case of anaphylaxis caused by matsutake mushroom (Tricholoma matsutake) ingestion.

BACKGROUND: Anaphylaxis is one of the severest forms of allergic diseases. Some kinds of mushroom are known as causative allergens in food anaphylaxis. Matsutake mushroom (Tricholoma matsutake) is a typical edible mushroom available in autumn in Japan. We encountered an 8-year-old Japanese girl who developed anaphylaxis after ingesting matsutake mushrooms. METHODS: We studied the case in detail, by measuring specific IgE antibodies and conducting skin tests, to confirm the diagnosis. We also detected seven cytokines and chemical mediators in the blood in order to study the pathophysiology of the anaphylaxis. RESULTS: We diagnosed anaphylaxis caused by ingestion of matsutake mushrooms based on the following. A skin prick test showed a positive reaction to matsutake mushroom, and specific IgE antibody for matsutake mushroom extract was detected in the patient's serum by fluorometric ELISA. Blood levels of chemical mediators including histamine, ECP, tryptase and cytokines such as IL-6, IL-5 and IL-10 but not IFN-gamma also increased significantly during the allergic episode. CONCLUSIONS: We demonstrated that chemical mediators including histamine, tryptase and ECP as well as several cytokines were involved significantly during the episode of anaphylaxis. In addition, eosinophils as well as mast cells played significant roles in the anaphylaxis. Furthermore, CD4+CD25+ T regulatory cells that released IL-10 were likely activated during the anaphylaxis. Matsutake mushroom should be considered as a causative allergen in food anaphylaxis.

Adrenergic Agonists↗

Distribution of two types of mast cells in the nasal mucosa after chemosurgical treatment of allergic rhinitis using trichloroacetic acid.

To evaluate the efficacy of chemosurgery using trichloroacetic acid (TCA) for allergic rhinitis, two types of tissue mast cells [tryptase-positive, chymase-negative mast cells (MCT) and tryptase-positive, chymase-positive mast cells (MCTC)] in the nasal turbinate mucosa were immunohistochemically identified and their distribution was assessed in clinical cases of patients who underwent unilateral TCA treatment. A comparison of the number of MCT and MCTC between the treated and nontreated sides indicates that both types of mast cells are significantly decreased in number in the treated side both in epithelial and lamina propria layers. The results indicate that TCA treatment was effective in suppressing MCT infiltration, regarded as a major cause of antigen-dependent allergy.

Administration, Topical↗

Azelastine reduces mediators of inflammation in patients with nasal polyps.

Nasal polyps affect approximately 4% of the population in the western world. The etiology of this disease is unknown, although inflammatory mechanisms may play an important role. In preceding studies we and others have shown that besides H1-antagonism, azelastine influences the immigration and activation of inflammatory cells. In this open label study in 16 patients with nasal polyps and perennial mite-allergic rhinitis, the effect of azelastine nasal spray twice daily 0.14 mg to each nostril on recurrence of nasal polyposis after endonasal surgery was evaluated. One patient dropped out after 3 months, unwilling to take further medication. Clinical and laboratory data of 15 patients were recorded over 25 weeks in a total of seven visits. Of these one patient needed nasal budesonide during the 4 weeks between visits 3 and 4. All other patients did not take any steroids before inclusion into the trial or during the 6-month observation period. Concentrations of eosinophil cationic protein (ECP) for eosinophils, myeloperoxidase (MPO) for neutrophils and tryptase for mast cells were determined in nasal secretions before and after eight and 25 weeks of treatment using double antibody radioimmunoassays, because these have been demonstrated to be good inflammatory markers in nasal diseases. Mean concentrations of MPO decreased from 2724 ng/mL to 1610 ng/mL (p = 0.0015) over the entire treatment period. ECP decreased from 458 ng/mL to 264 ng/mL (p = 0.0342). Tryptase decreased from 37.9 ng/mL to 22.4 ng/mL (p = 0.0574). These data were consistent with a significant decrease in clinical symptoms. Thus, azelastine seems to have an inhibitory effect on eosinophil and neutrophil activation in patients with nasal polyps and mite allergy.

Administration, Inhalation↗

Corticotropin-releasing hormone and the blood-brain-barrier.

Increased blood-brain-barrier (BBB) permeability precedes any clinical or pathologic signs and is critical in the pathogenesis of multiple sclerosis (MS) and brain metastases. CD4+ TH1 cells mediate demyelination in MS, but how they get sensitized and enter the brain to induce brain inflammation remains obscure. TH2 cytokines associated with allergic disorders have recently been implicated in MS, while genes upregulated in MS plaques include the mast cell-specific tryptase, the IgE receptor (Fc-epsilon-RI) and the histamine-1 receptor. Mast cell specific tryptase is elevated in the CSF of MS patients, induces microvascular leakage and stimulates protease-activated receptors (PAR), leading to widespread inflammation. BBB permeability, MS and brain metastases appear to worsen in response to acute stress that leads to the local release of corticotropin-releasing hormone (CRH), which activates brain mast cells to selectively release IL-6, IL-8 and vascular endothelial growth factor (VEGF). Acute stress increases BBB permeability that is dependent on CRH and mast cells. Acute stress shortens the time of onset of experimental alleric encephalomyelitis (EAE) that does not develop in W/W mast cell deficient or CRH -/- mice. Brain mast cell inhibition and CRHR antagonists offer novel therapeutic possibilities.

Animals↗

Immunoglobulin-E-bearing cells in skin biopsies of horses with insect bite hypersensitivity.

The aim of the present study was to investigate, with immunohistochemistry and in situ hybridisation, if immunoglobulin-E (IgE) and mast cells are involved in the pathogenesis of insect bite hypersensitivity (IBH), an allergic dermatitis of horses. In tissue sections fixed in paraformaldehyde (PFA) for <24 h, significantly more IgE protein-bearing cells were found in the dermis and epidermis of acute and chronic IBH lesions than in skin biopsies from healthy horses (medians = 466, 236 and 110 cells/mm2, respectively; P < or = 0.01). More IgE-mRNA positive (+) cells were observed in the dermis of acute IBH lesions than in the dermis of healthy skin (median = 2.8 vs. 0.0 cells/mm2; P < or = 0.01). Significantly, more mast cells were detected with metachromatic (median = 160 vs. 62 cells/mm2; P < or = 0.001) and tryptase-specific stainings (median = 120 vs. 69 cells/mm2; P < or = 0.001) in the dermis of acute IBH biopsies compared to healthy skin. No chymase+ mast cells were found in any skin biopsy. IBH lesions fixed in PFA for >24 h were compared to dermatomycosis (DM) lesions; IBH biopsies contained a similar number of IgE-protein+ cells to DM biopsies (median = 249 vs. 192 cells/mm2; P = 0.08) but had significantly more IgE-mRNA+, metachromatic and tryptase+ mast cells than DM biopsies. This study suggests an involvement of IgE-mediated immune reactions in the pathogenesis of IBH as well as, sometimes, in dermatomycosis. Using double labelling, cells which expressed IgE protein and contained mast cell enzymes were detected.

Animals↗

Clinical and biologic diversity of leukemias occurring in patients with mastocytosis.

Patients with systemic mast cell (MC) disease, but not those with cutaneous mastocytosis, are at a high risk (10-30%) to develop life-threatening myelogenous malignancies. In a significant proportion of cases, myeloid leukemias occur. Using conventional criteria, such leukemias resemble acute myeloid leukemia (AML), chronic myeloid leukemia (CML), or myelomonocytic leukemia (CMML). Mast cell leukemia (MCL) may also occur. Myeloid leukemias (AML, CML, CMML) can develop in indolent or aggressive mastocytosis (skin lesions present or absent) with a variable prephase of MC disease. By contrast, MCL (typically without skin lesions) often develops on a "de novo" basis, and, if at all recognized, a prephase resembling (malignant) mastocytosis, is short. MCL differs from myeloid leukemias (AML, CML, CMML) by morphologic and phenotypic cellular characteristics. In fact, MCL are strongly tryptase-positive, c-kit-positive, myeloperoxidase (MPO) -negative neoplasms with variable metachromasia and chloroacetate esterase expression, whereas an MPO-positive, tryptase-negative phenotype supports the diagnosis of a myeloid non-MC lineage disease. Thus, MCL, but also myeloid non-MC lineage leukemias can develop in patients with (systemic) mastocytosis. Little is known, however, about the pathophysiologic basis of co-evolution. In the present article, the concomitant occurrence of mastocytosis and leukemia is discussed in the light of the literature and of concepts proposed to explain the biologic basis of this phenomenon.

Acute Disease↗

IL-16 regulation of human mast cells/basophils and their susceptibility to HIV-1.

AIDS patients often contain HIV-1-infected mast cells (MCs)/basophils in their peripheral blood, and in vivo-differentiated MCs/basophils have been isolated from the blood of asthma patients that are HIV-1 susceptible ex vivo due to their surface expression of CD4 and varied chemokine receptors. Because IL-16 is a ligand for CD4 and/or an undefined CD4-associated protein, the ability of this multifunctional cytokine to regulate the development of human MCs/basophils from nongranulated progenitors residing in cord or peripheral blood was evaluated. After 3 wk of culture in the presence of c-kit ligand, IL-16 induced the progenitors residing in the blood of normal individuals to increase their expression of chymase and tryptase about 20-fold. As assessed immunohistochemically, >80% of these tryptase(+) and/or chymase(+) cells expressed CD4. The resulting cells responded to IL-16 in an in vitro chemotaxis assay, and this biologic response could be blocked by anti-IL-16 and anti-CD4 Abs as well as by a competitive peptide inhibitor corresponding to a sequence in the C-terminal domain of IL-16. The additional finding that IL-16 induces calcium mobilization in the HMC-1 cell line indicates that IL-16 acts directly on MCs and their committed progenitors. IL-16-treated MCs/basophils also are less susceptible to infection by an M/R5-tropic strain of HIV-1. Thus, IL-16 regulates MCs/basophils at a number of levels, including their vulnerability to retroviral infection.

Antiviral Agents↗

IL-9 enhances the growth of human mast cell progenitors under stimulation with stem cell factor.

We examined the effects of IL-9 on human mast cell development from CD34(+) cord blood (CB) and peripheral blood cells in serum-deprived cultures. IL-9 apparently enhanced cell production under stimulation with stem cell factor (SCF) from CD34(+) CB cells. A great majority of the cultured cells grown with SCF + IL-9 became positive for tryptase at 4 wk. In methylcellulose cultures of CD34(+) CB cells, IL-9 increased both the number and size of mast cell colonies grown with SCF. Furthermore, SCF + IL-9 caused an exclusive expansion of mast cell colony-forming cells in a 2-wk liquid culture of CD34(+) CB cells, at a level markedly greater than for SCF alone. Clonal cell cultures and RT-PCR analysis showed that the targets of SCF + IL-9 were the CD34(+)CD38(+) CB cells rather than the CD34(+)CD38(-) CB cells. IL-9 neither augmented the SCF-dependent generation of progeny nor supported the survival of 6-wk-cultured mast cells. Moreover, there was no difference in the appearance of tryptase(+) cells and histamine content in the cultured cells between SCF and SCF + IL-9. The addition of IL-9 increased numbers of mast cell colonies grown with SCF from CD34(+) peripheral blood cells in children with or without asthma. It is of interest that mast cell progenitors of asthmatic patients responded to SCF + IL-9 to a greater extent than those of normal controls. Taken together, IL-9 appears to act as a potent enhancer for the SCF-dependent growth of mast cell progenitors in humans, particularly asthmatic patients.

Adjuvants, Immunologic↗

Expression of the alphaEbeta7 integrin by mast cells in rheumatoid synovium.

OBJECTIVE: Rheumatoid synovitis is characterized by a mast cell response in which tryptase containing mast cells (MCT) associate with T lymphocyte infiltration, and tryptase and chymase containing mast cells (MCTC) correlate more closely with tissue damage or repair events. We investigated expression of the alphaEbeta7 integrin and its ligand E-cadherin in rheumatoid and normal synovium and compared this expression to synovial mast cell responses. METHODS: Immunohistochemical analysis was used to determine the expression of alphaEbeta7 and E-cadherin in rheumatoid (n = 17) and normal (n = 6) synovium. The density of MCT and MCTC mast cell subsets was compared to the density of alphaEbeta7 positive mast cells. RESULTS: The mean density of alphaEbeta7 positive cells in rheumatoid synovia was 25.2 cells/mm2 (range 0.3-102.9), of which 26.7% (range 0-68.6%) were mast cells. A mean of 11.9% (range 0-30.4%) of rheumatoid synovial mast cells expressed alphaEbeta7 compared to 0% in normal synovium (p < 0.0001). There was a strong correlation between the density of alphaEbeta7 positive cells and the total mast cell density in rheumatoid synovium (r2= 0.74). alphaEbeta7 positive mast cell density correlated significantly with the MCT subset density (r2 = 0.5, p = 0.014), but not with the MCTC subset density. E-cadherin expression was increased in rheumatoid compared with normal synovium, but did not colocalize or correlate with alphaEbeta7 expression. CONCLUSION: These results indicate a role for alphaEbeta7 in the mast cell response that occurs in rheumatoid synovitis, in particular the MCT mast cell subset expansion associated with inflammatory events and interactions with infiltrating lymphocytes.

Arthritis, Rheumatoid↗

[The relation between expression of basic fibroblast growth factor and mast cells in pterygium].

OBJECTIVE: To examine the expression and distribution of basic fibroblast growth factor (bFGF) and mast cells in pterygium, and evaluate its effects in the pterygium formation and progression. METHOD: The expression of bFGF and mast cell tryptase in 17 primary pterygia, 6 recurrent pterygia and 6 normal conjunctival specimens were studied. The mast cell count and bFGF expression situation were observed. RESULTS: The bFGF was specifically localized in the epithelium, blood vessels and a subset of connective tissue cells. The bFGF expression was increased in the recurrent pterygium. The numbers of infiltrating mast cells (five 400 x sights) were (45.47 +/- 5.50) cells and (48.83 +/- 3.19) cells in the primary and recurrent pterygium respectively. In the comparisons between the cells in the pterygium (primary and recurrent) and (4.24 +/- 2.36) cells in the normal connective tissue, there were significant differences (F = 200.3128; q = 26.6762, 23.7341; P < 0.05). The shape and distribution of all the tryptase-positive cells (mast cells) in the pterygium tissues were similar to that of the cells with bFGF expression in the connective tissue. And the majority of bFGF-positive cells (87.54 +/- 3.60)% were similar to that of mast cells in the connective tissue. CONCLUSIONS: All infiltrating mast cells in pterygium have bFGF-positive expression. The bFGF expression is increased in the epithelium, blood vessels and infiltrating mast cells of the pterygium, and may contribute to the formation and progression of a pterygium.

Adult↗

Increased expression of intercellular adhesion molecule 1 in relation to mast cells in the bladder of interstitial cystitis patients.

Interstitial cystitis (IC) is a sterile, painful bladder disorder, often associated with inflammation. A defective urothelium and activated mast cells have been implicated in the pathophysiology of IC. Mast cells have been reported to induce the expression of intercellular adhesion molecules (ICAM) that are considered a necessary first step for the initiation of inflammation. We investigated the presence of ICAM-1 and its association with bladder mast cells in IC patients and controls in order to further understand their role in the pathophysiology of IC. Bladder tissue was fresh frozen and 7m section were cut using a cryostat. Immunocytochemical detection was carried out with monoclonal antibodies directed against anti-ICAM1 and tryptase. Twenty-one biopsies from women with IC and two from normal tissue from radical cystectomies (control) were analyzed. All IC samples were strongly positive for ICAM-1, exclusively in capillaries. Control samples were only faintly positive in fewer capillaries. Numerous mast cells were identified in the positive regions with toluidine blue or tryptase immunocytochemistry. This work may help explain why many IC patients develop sterile inflammation. It may also provide evidence further explaining the role of bladder mast cells in the pathophysiology of IC.

Journal Article↗

Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit-ligand in long-term culture.

In the murine system, a number of cytokines (including interleukin-3 [IL-3], IL-4, and stem cell factor [SCF]) promote the growth of mast cells (MCs). However, so far little is known about factors controlling differentiation of human MCs. Recent data suggest that human MCs express receptors (R) for SCF. The aim of the present study was to investigate whether recombinant human (rh) SCF induces differentiation of human MCs from their precursor cells. For this purpose, bone marrow (BM; normal donors, n = 6) and peripheral blood (PB; normal donors, n = 11) mononuclear cells (MNC) were cultured in the presence of rhSCF, rhIL-3, rhIL-4, rhIL-9, recombinant human macrophage colony-stimulating factor (rhM-CSF), or control medium in long-term (8 weeks) suspension cultures. After 4 weeks, up to 5% of the MNC (BM and PB) cultured in the presence of rhSCF, but not in the presence of other cytokines, were found to exhibit the characteristics of MCs. These MCs expressed the YB5.B8-reactive domain of the SCF R as well as IgE R, as determined by combined toluidine blue/immunofluorescence staining. Myeloid antigens, likewise expressed on human basophils (ie, CD11b, CDw65, and Bsp-1), could not be detected on these cells. Furthermore, rhSCF, but not rhIL-3, rhIL-4, rhIL-9, or rhM-CSF, induced dose- and time-dependent increases in the formation of cellular tryptase (an MC-specific enzyme) (rhSCF [100 ng/mL], 1,308 +/- 679 ng/mL v control medium, 18 +/- 6 ng/mL tryptase on day 35 of PB cell cultures), as well as an increase in cellular histamine. After 6 to 8 weeks, when other mature hematopoietic cells decreased, MCs still could be detected in culture, with up to 40% of all cells being MCs. To test whether rhSCF also activates tissue MCs, we performed histamine release experiments (dispersed tissue; lung, n = 3; uterus, n = 3). SCF was found to enhance (by up to 3.4-fold) the capacity of the MCs to release histamine upon cross-linkage of IgE R with anti-IgE. Together, these observations suggest that rhSCF induces in vitro differentiation of human MCs from their BM and PB precursor cells in long-term culture and upregulates MC releasability.

Antibodies, Monoclonal↗

Nasal lavage fluid examination in diagnostics of occupational allergy to chloramine.

OBJECTIVES: Chloramine T is a known sensitising agent in the occupational environment of health care workers. In cases of occupational hazards induced by this agent, a clinical history may be far from conclusive, hence appropriate provocation tests are absolutely essential. The aim of the study was to evaluate the usefulness of the nasal challenge test in diagnostics of respiratory allergy to chloramine T. MATERIALS AND METHODS: A single-blind, placebo-controlled study was conducted in 6 subjects with chloramine T asthma and rhinitis. Two control groups comprised 7 atopic subjects with asthma and rhinitis and 6 healthy persons. All the controls had negative results of skin prick tests with chloramine T and none displayed any respiratory symptoms under exposure to the agent. A "nasal pool" technique was used to evaluate morphological and biochemical parameters (mast cell tryptase, eosinophil cationic protein, permeability index) in nasal washings before and 30 min, 4 h and 24 h after the provocation with chloramine T and placebo. RESULTS: A significant increase was found in the total count and percentage of eosinophils and basophils, albumin, tryptase and eosinophil cationic protein levels in the nasal lavage fluid from patients with chloramine T respiratory allergy when compared to both control groups. Also a dual asthmatic reaction in 4 patients and an isolated late reaction in 2 cases were observed in chloramine-sensitive subjects. CONCLUSIONS: The results indicate the applicability of the "nasal pool" technique as a diagnostic procedure in chloramine T-induced airway allergy.

Adult↗

The human heart as a shock organ in anaphylaxis.

Human mast cells, by elaborating vasoactive mediators and cytokines, are the primary effector cells of anaphylaxis. A body of evidence implicates human heart mast cells (HHMCs) in anaphylaxis. These cells have been identified perivascularly, in dose proximity to myocytes and in the arterial intima in human heart tissue. The membrane surface of mast cells from human heart tissue of patients undergoing cardiac transplantation expresses the high affinity receptors for IgE (FcepsilonRI) and C5a receptors. Activation of HHMCs in vitro with anti-IgE or anti-FcepsilonRI induced the release of preformed mediators (histamine, tryptase and chymase) and the de novo synthesis of LTC4 (approximately equal to 18 ng/10(6) cells) and PGD2 (approximately equal to 18 ng/10(6) cells). Complement activation and anaphylatoxin formation occur during anaphylaxis in human. C5a caused rapid release of histamine and tryptase from HHMCs. These cells are activated in vitro by therapeutic (general anaesthetics, protamine, etc.) and diagnostic agents (radio contrast media, etc.) that may cause non-IgE-mediated anaphylactic reactions. Administration of low concentrations of histamine and cysteinyl leukotrienes in subjects undergoing diagnostic catheterization caused significant systemic and coronary haemodynamic effects. Taken together, these results indicate that the human heart can be both the site and the target of anaphylactic reactions.

Anaphylaxis↗

Relevance of mast cells and hepatic lobule innervation to liver injury.

Chronic liver diseases commonly result in liver fibrosis, and eventually liver cirrhosis. In the last decade, a new theory explaining liver fibrosis has been established. Accordingly, the development of liver fibrosis due to chronic liver diseases is thought to be mediated by inflammatory cells. They release fibrogenic mediators such as transforming growth factors (TGF)-beta, which are considered to be responsible for the activation and transformation of fat-storing cells. Recently, the involvement of mast cells and peripheral and autonomic nervous system in the fibrogenesis has been suggested. This study was aimed to establish the presence and distribution of mast cells and nerve fibers in the rat liver in the light of their implication in liver inflammatory and fibrotic disorders. Mast cells and afferent (sensory) fibers were detected immunohistochemically. An immunofluorescent method was applied to demonstrate tryptase and serotonin (SER) in the mast cells, while the primary sensory neuronal processes were identified by using antibodies against their marker calcitonin gene-related peptide (CGRP) and the proinflammatory mediator substance P (SP). The portal tracts and fibrous septa contained numerous mast cells, which exhibited strong immuno-reactivity to tryptase and SER. SER-positive nerve fibers were also found. It is generally accepted that no nerve fibers are present in the hepatic lobules, but the current investigation clearly demonstrates availability of CGRP-, SP, and SER-immunoreactive nerve fibers there. Our results indicate that in the rat liver portal tracts and hepatic lobules there are numerous mast cells, sensory and autonomic nerve fibers, which may be involved in liver injury by the inflammatory mediators they release.

Animals↗

Morphological analysis of cell subpopulations within carotid atherosclerotic plaques.

Atherosclerosis is considered a chronic inflammatory process, prompted by lipid accumulation and propagated by cell-mediated mechanisms. The present work was undertaken to clarify this process by characterizing cellular components of inflammatory infiltrate localized within atheroma. Cryostat sections of atherosclerotic lesions obtained from human carotid endarterectomy were analysed immunohistochemically by using monoclonal and polyclonal antibody directed against T cell subpopulations (CD3, CD4, CD8), B cells (CD20), plasma cells (CD138), macrophages (CD14), mast cells (anti-tryptase). Our results assess that T cells are the predominant cell type among plaque infiltrating inflammatory cells. B cells were detected near the lipid core of atheroma and clusters of plasma cells were observed within cellular infiltrates in most plaques. Numerous tryptase positive mast cells were noticed in many areas of complicated lesions. Our results indicate the presence of many inflammatory cells within type V and VI atherosclerotic plaques, suggesting the involvement of those cells in plaque progression. In fact it was previously shown that stability of atherosclerotic lesions is influenced by mast cell-released matrix metalloproteinases which induce plaque rupture and by cytokines and chemokines which increase local inflammatory response and are produced by lymphocytes and macrophages.

Aged↗