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PubMed1994

Assessment of inflammation in noninfectious chronic maxillary sinusitis.

BACKGROUND AND AIM: Pathologic examination of the sinus mucosa and titration of inflammatory mediators in the sinus fluid were carried out to characterize inflammation in chronic sinusitis and determine whether patients with chronic allergic rhinitis (CAR) and sinusitis differ from patients with chronic nonallergic rhinitis (CNAR) and sinusitis. METHODS: Nine control subjects (patients requiring ear, nose, and throat surgery not related to sinusitis), 12 patients with CAR and sinusitis, and 13 patients with CNAR and sinusitis were investigated. Eosinophil cationic protein, tryptase, myeloperoxidase, histamine, and prostaglandin D2 were measured in the sinus lavage fluids, and cells were enumerated. The cellular infiltrate was studied by immunohistochemistry with monoclonal antibodies against eosinophil cationic protein (eosinophils), tryptase (mast cells), neutrophil elastase (neutrophils), CD3 (lymphocytes), CD68 (macrophages), and proliferating cell nuclear antigens. RESULTS: Neutrophils were not increased in sinusitis. In comparison with control subjects, patients with CAR and CNAR with sinusitis showed significant increases in eosinophils and macrophages in biopsy specimens and in eosinophil cationic protein in sinus lavage fluids. In comparison with patients with CNAR, patients with CAR had an increased number of intraepithelial mast cells and lymphocytes. CONCLUSIONS: These findings suggest that patients with CNAR and sinusitis can be distinguished from patients with CAR and sinusitis, which resembles nonallergic rhinitis with eosinophilia syndrome.

Adolescent↗
PubMed1989

Selective isocoumarin serine protease inhibitors block RNK-16 lymphocyte granule-mediated cytolysis.

Granules that are potently cytolytic in vitro can be obtained from cytotoxic lymphocytes that kill virally infected cells and tumor cells. These granules contain pore-forming proteins and several serine proteases. Here we indicate that at least two different proteases participate in the lysis mediated by granule proteins from RNK-16 rat leukemia cells. We report twelve different mechanism-based or "suicide" isocoumarin serine protease inhibitors which have different 3- and 7-substituents that confer selectivity and reactivity towards either the chymotrypsin- ("chymase") or trypsin-like ("tryptase") protease activities of RNK-16 cells. Second order inhibition rates of inactivation (kobsd/[I]) for the RNK-16 granule proteases ranged between 164 and 22,640 M-1s-1. These new, specific and highly reactive isocoumarin serine protease inhibitors also abrogated the cytolysis mediated by lymphocytes granule proteins. The eight inhibitors with large hydrophobic or basic substituents that conferred chymase or tryptase specificities were more effective at inactivating lytic function than the four elastase-directed inhibitors with smaller substituents. All twelve new isocoumarin inhibitors blocked cytolysis at lower concentrations than 3,4-dichloroisocoumarin, a potent general mechanism-based serine protease inhibitor that also blocks RNK-16 granule protease activities and lysis.

Animals↗
PubMedDate not supplied

Nasal lavage as a tool in assessing acute inflammation in response to inhaled pollutants.

The upper airway, especially the nose, is a major target of toxic damage. Nasal challenges followed by nasal lavage (NAL) have been applied to studies of hypersensitivity, in particular as a method to identify the allergen in patients with allergic situations such as rhinitis. The NAL method has not been extensively used to determine the effects of air pollutants on the upper airways in humans. Ozone is known to interact avidly with various tissues in the respiratory tract and to cause decrements in lung function tests. This oxidant pollutant has also been shown to induce inflammation in the lower airways of humans and animals. In this study, we have examined the effect of an acute (2 h) exposure of ozone at 0.4 ppm on the inflammatory response in the upper airways of 10 normal volunteers and compared these results to those obtained in the lower airways assessed by bronchoalveolar lavage (BAL). The results indicate significant increases in the number of polymorphonuclear neutrophils (PMN) in NAL immediately post exposure (7.7-fold). This increase is still detectable 18 h post exposure (6-fold) which is similar to the increase of PMN in BAL. Tryptase, released by mast cells was also increased in the NAL fluid immediately post exposure (2-fold). While the albumin level, which is an indicator of epithelial cell permeability, was elevated 18 h post exposure (1.5-fold), tryptase level, was not anymore elevated at that time point. Interestingly, several other markers of acute inflammation such as prostaglandin E2 (PGE2), C3a, urokinase-type plasminogen activator (U-PA), which were found to be significantly elevated in the BAL of the same group of subjects (18 h post exposure), were not elevated in the NAL either immediately post or 18 h post exposure. The level of uric acid, thought to be an important anti-oxidant molecule, was also unchanged in the NAL fluid but was elevated in the BAL fluid. Collectively the data suggest that NAL may serve as a sensitive and reliable technique to detect inflammation in the upper airways of subjects exposed to ozone. Moreover, in the case of this particular oxidant pollutant, the NAL seems to mirror the inflammatory response in the lower airways, 18 h post exposure, relative to the number of PMN and albumin levels.

Adult↗
PubMed2004

Role of mast cells and their mediators in failing myocardium under mechanical ventricular support.

BACKGROUND: Mast cells have been implicated in tissue remodeling and fibroblast stimulation. We explored the effect of mechanical support by left ventricular assist device (LVAD) in failing myocardium and looked into grade and distribution of interstitial fibrosis, mast cell density, mast cell phenotypes and basic fibroblast growth factor (bFGF) expression pre- and post-LVAD. METHODS: Myocardial tissue was obtained from 20 patients with end-stage cardiomyopathy at the time of LVAD implantation and LVAD removal and from 7 donor hearts not used for transplantation. Tissue sections were stained for mast cells using tryptase as a marker and the myocardial fibrosis was measured. Double staining for tryptase and chymase was performed for detection of chymase-positive mast cells. Fluorescent microscopy showed the relationship of mast cells to bFGF, and bFGF expression was quantified by Western blot. RESULTS: There was a significant increase in mast cells in heart failure vs normal myocardium. A secondary increase in mast cells occurred after long-term (>40 days) support compared with matched pre-LVAD samples (mean +/- SEM; 57.4 +/- 8.6 cells/10 fields vs 45.1 +/- 7.6 SEM cells/10 fields, p < 0.01). The secondary increase in mast cells was associated specifically with an increase in chymase-negative mast cells (p < 0.01). These findings are statistically significant with concurrent decreased expression of bFGF and decreased fibrosis in the same patient tissues (p < 0.01). CONCLUSIONS: We suggest that, under long-term support, there is a change in phenotypic expression in mast cells, which can alter fibroblast functions. The decreased myocardial bFGF levels might be the result of these phenotypically altered mast cells.

Adult↗
PubMed2004

Cetirizine and allopurinol as novel weapons against cellular autoimmune disorders.

Type 1, or cellular, immune response is characterized by overproduction of TNF-alpha, IFN-gamma, IL-1, IL-2 and IL-8 and is the underlying immune mechanism of psoriasis, alopecia areata, rheumatoid arthritis, Crohn's disease, multiple sclerosis, insulin-dependent diabetes mellitus and experimental autoimmune uveitis (EAU). Type 2 immune response is seen in antibody-mediated autoimmune diseases. Based on the pharmacokinetic effects of cetirizine and allopurinol, this paper introduces these two safe and inexpensive drugs as novel potential agents against cell-mediated autoimmune disorders. Cetirizine, supposed to inhibit DNA binding activity of NF-kappa B, inhibits the expression of adhesion molecules on immunocytes and endothelial cells and the production of IL-8 and LTB4, two potent chemoattractants, by immune cells. It induces the release of PGE2, a suppressor of antigen presentation and MHC class II expression, from monocyte/macrophages and reduces the number of tryptase positive mast cells in inflammation sites. Tryptase is a chemoattractant, generates kinins from kininogen, activates mast cells, triggers maturation of dendritic cells and stimulates the release of IL-8 from endothelial cells and the production of Th1 lymphokines by mononuclear immunocytes. Allopurinol is a free radical scavenger, suppresses the production of TNF-alpha and downregulates the expression of ICAM-1 and P2X(7) receptors on monocyte/macrophages. ICAM-1 serves as a ligand for LFA-1 (on T lymphocytes), allowing proper antigen presentation. P2X(7) receptors are thought to be involved in IL-1beta release, mitogenic stimulation of T lymphocytes and the probable cytoplasmic communication between macrophages and lymphocytes at inflammation sites. Allopurinol was markedly more effective than prednisolone in treating experimental autoimmune uveitis and in combination with cyclosporine suppressed the inflammatory reaction of this condition more effectively than either agent alone. As allopurinol is a competitive inhibitor of xanthine oxidase and decreases serum levels of uric acid, which is protective against multiple sclerosis, it should preferably be coadministered with uric acid precursors in the treatment of this condition. Cetirizine and allopurinol may prove of benefit in the treatment of various cellular autoimmune disorders.

Adjuvants, Immunologic↗
PubMed2006

Abrogation of allergic reactions by a bispecific antibody fragment linking IgE to CD300a.

BACKGROUND: Initiated and regulated by mast cells, allergic responses are balanced through an intricate network of positive and negative signals. We have recently shown that the inhibitory receptor CD300a is expressed on human mast cells and modulates a large array of their functions. OBJECTIVE: We sought to evaluate CD300a as a negative regulator of allergic inflammation in vivo by means of a bispecific antibody linking CD300a with IgE. METHODS: Bispecific antibody fragments were generated by chemical conjugation of Fab' fragments of anti-human IgE and CD300a (IE1H) and anti-mouse IgE and CD300a (IE1M). IgE-sensitized human mast cells were activated simultaneously with anti-IgE and IE1H. Phosphorylation of signaling proteins and calcium influx were evaluated by using fluorescence-activated cell sorting. Degranulation was assessed on the basis of tryptase and IL-4 release. IE1M was administered simultaneously with allergen challenge in 2 murine models of allergic disease. Passive cutaneous anaphylaxis was assessed by means of dye exudation. Experimental airway inflammation was assessed on the basis of tryptase and cytokine content, eosinophilic infiltration, and lung histology (hematoxylin and eosin and periodic acid-Schiff stain). RESULTS: IE1H potently inhibited IgE-mediated mast cell degranulation in a dose-dependent manner by inhibiting the signaling events induced by FcvarepsilonRI. IE1M completely abolished dye exudation in passive cutaneous anaphylaxis. IE1M abrogated allergic airway inflammation. CONCLUSION: Our results demonstrate that specific targeting of CD300a on mast cells is a potent strategy for inhibiting allergic reactions. CLINICAL IMPLICATIONS: This work demonstrates a potent approach for the therapy of allergic diseases.

Animals↗
PubMedDate not supplied

Tranilast reduces mesenteric vascular collagen deposition and chymase-positive mast cells in experimental diabetes.

The mast cell has a central role in the pathogenesis of fibrosis a common feature of diabetic microvascular complications. Increased mast cell numbers have been demonstrated in diabetic nephropathy in association with renal fibrosis, and diabetes acutely increases mast cell infiltration in the mesentery. Antimast cell agents such as tranilast may ameliorate the acute vascular changes in diabetes due to stabilisation of mast cells and/or reduction in mast cell numbers. After 3 weeks of streptozotocin diabetes, light microscopy techniques were used to estimate mesenteric vessel fibrosis and mast cell infiltration. Mast cells were identified by toluidine blue staining and tryptase, chymase and TGF-beta immunohistochemistry in three study groups of rats: control, diabetic and plus tranilast. Diabetes was associated with an increase in both mesenteric vessel fibrosis and mast cell numbers. Administration of tranilast to diabetic rats reduced mesenteric vessel fibrosis and this was associated with a reduction in chymase-positive mast cells. These changes were independent of mast cell TGF-beta and were not associated with a reduction in tryptase-positive mast cells. The amelioration of diabetes-induced vessel fibrosis may be due to a reduction in the liberation of angiotensin II by inhibiting mast cell chymase.

Animals↗
PubMed2005

Buffy coat preparation is a convenient source of progenitors for culturing mature human mast cells.

Mast cells are unique immune cells that release a spectrum of chemical mediators contributing to the inflammatory symptoms of allergic disorders. Mature mast cells have recently been cultured from CD34(+) progenitors isolated from fresh umbilical cord blood and adult peripheral blood. In the current study, we investigated whether buffy coat preparations, which are readily available from blood banks, could be used as a convenient and more abundant source of progenitors for culturing human mast cells. We were able to culture a homogeneous population of human mast cells from progenitor cells isolated from human buffy coat. Morphologically, our cultured mast cells contained abundant cytoplasmic granules which stained positively using antibodies against human mast cell tryptase and, to a lesser extent, with those against human mast cell chymase. Functionally, these cultured mast cells responded to anti-human-IgE by releasing histamine in a dose-dependent manner after sensitization with human IgE. Taken together, buffy coat preparations can be a convenient source for culturing human mast cells which are predominantly tryptase positive only and express functional high-affinity IgE receptors.

Blood Cells↗
PubMed2007

Effects of topical formoterol alone and in combination with budesonide in a pollen season model of allergic rhinitis.

BACKGROUND: beta(2)-Agonists may exert mast cell stabilizing and anti-plasma exudation effects. While available data suggest no or only marginal effects of beta(2)-agonists on symptoms of allergic rhinitis, little is known about whether these drugs may add to the efficacy of anti-rhinitis drugs. OBJECTIVE: To examine effects of a beta(2)-agonist, alone and in combination with an intranasal glucocorticosteroid, on symptoms and signs of allergic rhinitis. METHODS: Patients were examined in a pollen season model. Budesonide 64 microg, alone and in combination with formoterol 9 microg, as well as formoterol 9 microg alone was given in a placebo-controlled and crossover design. After 7 days of treatment, the patients received allergen challenges for 7 days. Symptoms and nasal peak inspiratory flow (PIF) were recorded. Nasal lavages with and without histamine were carried out at the end of each challenge series. These lavages were analysed for tryptase, eosinophil cationic protein (ECP), and alpha(2)-macroglobulin as indices of mast cell activity, eosinophil activity, and plasma exudation, respectively. RESULTS: Budesonide reduced symptoms of allergic rhinitis and improved nasal PIF in the morning, in the evening as well as post allergen challenge. Formoterol alone did not affect symptoms or nasal PIF and did not affect the efficacy of budesonide. Tryptase, ECP, and alpha(2)-macroglobulin were significantly reduced by budesonide. Formoterol alone did not affect these indices and did not affect the anti-inflammatory effect of budesonide. CONCLUSION: The present dose of formoterol does not affect symptoms and inflammatory signs of allergic rhinitis and does not add to the efficacy of topical budesonide.

Administration, Intranasal↗
PubMed2006

The involvement of mast cells and mast cell proteinases in the intestinal response to equine cyathostomin infection.

Cyathostomins (Cyathostominae) are regarded as the most pathogenic equine nematode worldwide. These nematodes are difficult to control in equine populations due to emerging anthelmintic resistance and evasion of encysted larval cyathostomins to regular modern anthelmintics. Mast cells and their proteinases have been shown to play a role in the mammalian immune response to nematode infections. Involvement of mast cells and mast cell proteinases in the equine immune response to cyathostomin infection is proposed. A technique was established to perform immunohistochemical staining using polyclonal rabbit anti-equine mast cell proteinase-1 (eqMCP-1) and anti-equine tryptase on formalin-fixed large intestinal sections, from horses classified as cyathostomin positive and negative at the time of death based upon larval enumeration. Quantitative analysis of antibody labelled mast cells was used to detect mast cell proteinases in equine large intestinal sections positive and negative for cyathostomin larvae. This demonstrated an increase in equine tryptase labelled mucosal and submucosal mast cells in cyathostomin positive horses. This study has established an immunohistochemical technique to demonstrate mast cell proteinases in formalin-fixed large intestinal sections. This technique may be used to determine possible involvement of mast cells and their proteinases in the equine immune response to cyathostomin larvae. Further studies are required to define a specific role.

Animals↗
PubMed2000

Evidence for the activation of PAR-2 by the sperm protease, acrosin: expression of the receptor on oocytes.

Proteinase-activated receptor-2 (PAR-2) is a member of a family of G-protein-coupled, seven-transmembrane domain receptors that are activated by proteolytic cleavage. The receptor is expressed in a number of different tissues and potential physiological activators identified thus far include trypsin and mast cell tryptase. Acrosin, a trypsin-like serine proteinase found in spermatozoa of all mammals, was found to cleave a model peptide fluorescent quenched substrate representing the cleavage site of PAR-2. This substrate was cleaved with kinetics similar to those of the known PAR-2 activators, trypsin and mast cell tryptase. Acrosin was also shown to induce significant intracellular calcium responses in Chinese hamster ovary cells stably expressing intact human PAR-2, most probably due to activation of the receptor. Immunohistochemical studies using PAR-2 specific antibodies indicated that the receptor is expressed by mouse oocytes, which suggests that acrosin may play additional role(s) in the fertilization process via the activation of PAR-2 on oocytes.

Acrosin↗
PubMed2001

Mast cell involvement in interstitial cystitis: a review of human and experimental evidence.

Interstitial cystitis (IC) is a heterogeneous syndrome of unknown etiology. Altered bladder glycosaminoglycans lining and bladder mastocytosis have been documented in IC. The objective of this article is to critically examine the published data on bladder mastocytosis in clinical, experimental, and animal studies, with particular emphasis on morphologic evidence of mast cell increase and activation. The literature on bladder mastocytosis and mast cell activation in IC is critically reviewed with particular reference to staining methodology, tryptase immunoreactivity, and electron microscopy. Data from humans and animal models of IC are included. Mastocytosis in IC is best documented by tryptase immunocytochemical staining. Standard surgical stains such as Giemsa and toluidine blue routinely underestimate the degree of mastocytosis. Mast cells are 6- to 8-fold higher in the detrusor compared with controls in "classic IC," and 2- to 3-fold higher in "nonulcerative" IC. Detrusor mastocytosis occurs in both classic and nonulcer IC. Mucosal mast cell increase is present in nonulcerative IC. Mast cell activation without typical exocytosis occurs in the mucosa and submucosa. Activation of mast cells, irrespective of bladder location or degree of mastocytosis, is significant. Mast cell-derived vasoactive and proinflammatory molecules may contribute to the pathogenesis of IC.

Animals↗
PubMed1990

Human conjunctival mast cells: distribution of MCT and MCTC in vernal conjunctivitis and giant papillary conjunctivitis.

The distribution and concentration of human tryptase-positive, chymase-negative mast cells (MCTS) and tryptase-positive, chymase-positive mast cells (MCTCS) were examined in conjunctival biopsy specimens from subjects with active vernal conjunctivitis (VC; n = 7), giant papillary conjunctivitis (GPC; n = 6), and allergic conjunctivitis (AC; n = 5), and from asymptomatic soft-contact lens wearers (SCL; n = 6) and normal control individuals (n = 19). Carnoy's fixed tissue sections were stained by a double immunohistochemical method using a biotinylated mouse monoclonal antichymase antibody with immunoperoxidase, followed by an alkaline phosphatase-conjugated mouse monoclonal antitryptase antibody. Epithelial mast cells (MCs) were found in all VC specimens (96% MCTCs) and in three GPC specimens (100% MCTCS) but in none of the other groups. In the substantia propria, MCTCS were the predominant type of MC observed in all specimens, accounting for 95% of the total MCs in the normal control group and 100% of the total MCs in the subjects with GPC, AC, and SCL. No significant differences were found in the total MC concentration of the substantia propria among the normal control subjects (11,054 +/- 6327 MCs per cubic millimeter), subjects in the SCL group (13,168 +/- 4685 MCs per cubic millimeter), subjects with GPC (17,313 +/- 8500 MCs per cubic millimeter), and subjects with AC (15,380 +/- 5660 MCs per cubic millimeter). In subjects with VC, the percentage of MCTs (18% +/- 13%) and the total MC concentration (24,689 +/- 18,978 MCs per cubic millimeter) in the substantia propria were significantly increased as compared to the normal control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1994

Analysis of cellular and biochemical constituents of induced sputum after allergen challenge: a method for studying allergic airway inflammation.

To determine whether analysis of the constituents of induced sputum permits detection of changes provoked by aerosolized antigen challenge, we performed sputum induction (20-minute inhalation of aerosolized 3% saline solution) before and after aerosolized allergen challenge in eight subjects with asthma. Total cell counts and cell differentials of nonsquamous cells in induced sputum samples were determined after the samples were homogenized in dithiothreitol. Centrifugation of the entire homogenized sputum sample yielded supernatant that could be analyzed for biochemical constituents. We found that the median percentage of eosinophils and neutrophils in induced sputum samples was significantly higher 4 hours after allergen challenge neutrophils in induced sputum samples was significantly higher 4 hours after allergen challenge than at baseline (12% vs 0.5%, p < 0.05; 30.5% vs 7.5%, p < 0.05) and remained high 24 hours after challenge. Median levels of eosinophil cationic protein and histamine in induced sputum supernatants were significantly higher 4 hours after challenge than at baseline (151.3 vs 39.8 ng/ml, p < 0.05; 19.4 vs 8.8 micrograms, p < 0.05) and remained significantly higher 24 hours after challenge. Tryptase was detectable in sputum from seven of the subjects, and in these subjects, we found a trend toward an increase in median tryptase levels 4 hours after allergen challenge (4.4 vs 2.2 U/L, p = 0.09). We conclude that analysis of induced sputum after aerosolized allergen challenge reveals changes in inflammatory cells and markers similar to those reported in bronchoalveolar lavage fluid and that sputum induction is a useful noninvasive method for studying allergic airway inflammation in asthma.

Administration, Inhalation↗
PubMed1995

Mast cell number and phenotype in chronic idiopathic urticaria.

BACKGROUND: Increased levels of histamine have been previously demonstrated in patients with chronic idiopathic urticaria. OBJECTIVE: The purpose of the study was to determine whether increased numbers of mast cells are present in lesional skin from such patients. METHODS: Mast cells have been quantified in lesional (n = 11) and nonlesional (n = 9) skin from patients with chronic idiopathic urticaria and compared with site-matched skin from healthy control subjects (n = 10). Mast cells were identified by using a sensitive, double-labeling immunohistochemical technique with specific monoclonal antibodies to mast cell tryptase and chymase and quantified under light microscopy. RESULTS: No significant differences in mast cell numbers from lesional, nonlesional, or control skin were observed (p > 0.1, Student's t test). In both patients with urticaria and control subjects, more than 99% of cutaneous mast cells contained tryptase and chymase. CONCLUSIONS: These data indicate that increased skin histamine in chronic idiopathic urticaria is not caused by increased mast cells and may alternatively reflect an increase in histamine content per mast cell, enhanced mast cell activation, or recruitment of basophils into skin in patients with chronic idiopathic urticaria.

Adult↗
PubMed1995

Products of arachidonic acid metabolism and the effects of cyclooxygenase inhibition on ongoing cutaneous allergic reactions in human beings.

BACKGROUND: There have been conflicting reports about the effects of inhibition of arachidonic acid metabolism on early- and late-phase cutaneous reactions. We re-examined this question with a unique nonsteroidal antiinflammatory drug, tenidap sodium. Tenidap sodium has been demonstrated in in vitro studies to inhibit cyclooxygenase, lipoxygenase, and cytokine production (interleukin-1, interleukin-6, tumor necrosis factor-alpha). METHODS: In a double-blind, randomized, crossover study, seven pollen-sensitive subjects ingested tenidap (120 mg, by mouth, daily) and placebo for 9 days with a 3-week washout period between treatments. On the eighth day they underwent allergen skin testing, measurable for up to 12 hours, and on the ninth day they underwent 5-hour skin chamber exposures to allergen and buffer. Chamber fluids were analyzed for cellular content, neutrophil granule protein release, cyclooxygenase and lipoxygenase arachidonic acid metabolites, histamine, and tryptase. RESULTS: Tenidap did significantly inhibit cyclooxygenase metabolites at both antigen and buffer sites but had no effect on histamine, tryptase, lipoxygenase metabolites, or granulocyte infiltration. Neutrophil granule release of lactoferrin was lower at the antigen site during tenidap administration, but there was no reduction of elastase release. Prostaglandin E2 and leukotriene E4 increased significantly at antigen sites compared with buffer sites during placebo administration and were the most prominent arachidonic acid metabolites detected. CONCLUSION: Tenidap, despite inhibiting cyclooxygenase release at antigen sites, had no effect on skin test responses to antigen or on antigen-induced mediator release or granulocyte infiltration. We conclude that cyclooxygenase metabolites are not important in the development of an allergic cutaneous inflammatory response.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Histochemical and functional characteristics of metachromatic cells in the nasal epithelium in allergic rhinitis: studies of nasal scrapings and their dispersed cells.

BACKGROUND: In allergic rhinitis, metachromatic cells in the nasal epithelium increase in number and are thought to play an important role in nasal allergic manifestation. METHODS: To determine immunohistochemical and functional characteristics of the metachromatic cells, nasal scrapings and their dispersed cells from patients with perennial allergic rhinitis were studied. RESULTS: Eighty-three percent of all metachromatic cells in dispersed cell preparations were tryptase-positive mast cells (MCT), 10% were tryptase-chymase-positive cells (MCTC), and 7% were negative (n = 10). The mean histamine chymase-positive cells (MCTC), and 7% were negative (n = 10). The mean histamine content per metachromatic cell was 1.9 +/- 2 pg. The histamine content and histamine release from nasal surface scrapings of patients sensitized with mite antigen were strongly correlated with the level of serum IgE antibody for mite antigen. The net histamine release from nasal scraping was antigen-dose-dependent (1:2 x 10(7) to 1:2 x 10(3) dilution), and the antigen stimulated release of up to 17% of cell-associated histamine within 5 to 7 minutes. Histamine release from nasal scrapings induced by calcium ionophore A23187 was up to 21% of cell-associated histamine within 2 to 4 minutes, but no histamine release was stimulated by compound 48/80, substance P, or poly-L-lysine. Histamine release from nasal scrapings was inhibited 46% (10(-5) mol/L) to 96% (10(-4) mol/L) by quercetin and 58% (10(-4) mol/L) to 72% (10(-3) mol/L) by sodium cromoglycate. CONCLUSIONS: These findings show the predominant characteristics of mast cells in the nasal epithelium in allergic rhinitis, and this information may be useful in relation to a therapeutic approach.

Adolescent↗
PubMed1998

IL-4- and IL-5-positive T lymphocytes, eosinophils, and mast cells in allergen-induced late-phase cutaneous reactions in atopic subjects.

It has previously been shown that cells mRNA+ for T(H2)-type cytokines (IL-4 and IL-5) infiltrate the site of allergen-induced cutaneous late-phase reactions (LPR) in atopic subjects. In this study we have used the same experimental model to identify the cell source of both IL-4 and IL-5 mRNA and protein product. Allergen-induced LPRs were provoked in the skin of atopic individuals and the sites microscopically examined at 6, 24, and 48 hours. Using single in situ hybridization and immunohistochemistry, we first showed that the numbers of IL-4 and IL-5 mRNA and protein product positive cells peaked at 24 hours. This coincided with the magnitude of the LPR. By double in situ hybridization/immunohistochemistry, we then established (in 24-hour biopsy specimens) that the percentage of CD3+ T lymphocytes, EG2+ eosinophils, and tryptase-positive mast cells that were either IL-4 or IL-5 mRNA+ was 19%, 24%, and 5% and 19%, 20%, and 5%, respectively. Conversely, the percentage of EG2+ and tryptase-positive cells that were IL-4 or IL-5 protein product positive were 62% and 53% and 72% and 29%, respectively. IL-4 and IL-5 protein did not colocalize to CD3+ cells. CD68+ macrophages were negative in both in situ hybridization and immunohistochemistry. With eosinophils we obtained direct evidence of time-dependent stimulus-induced IL-4 and IL-5 mRNA transcription by semiquantitative reverse transcription-polymerase chain reaction of cells incubated with either IgG- or sIgA-coated particles in vitro. Taken together, these experiments suggest that eosinophils, mast cells, and T cells all contribute in variable degrees to the expression of IL-4 and IL-5 in human cutaneous LPR. The failure to colocalize IL-4/IL-5 protein (as opposed to mRNA) to CD3+ cells is attributed to the inability of T lymphocytes to store and concentrate sufficient intracellular amounts of these cytokines to produce positive immunostaining.

Adult↗