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PubMed1990

Mast cells in cutaneous mastocytosis: accumulation of the MCTC type.

Lesional (n = 15) and non-lesional (n = 10) skin of subjects with mastocytosis was analysed for the distribution and concentration of trypase positive, chymase negative mast cells (MCT) and tryptase positive, chymase positive mast cells (MCTC) cells and compared to normal skin (n = 23) and non-lesional skin of subjects with unexplained anaphylaxis or flushing episodes (n = 6). Skin biopsies were fixed in Carnoy's fluid and subjected to double immunohistochemical staining with biotinylated mouse monoclonal anti-chymase antibody followed by alkaline phosphatase-conjugated mouse monoclonal anti-tryptase antibody. MCTC cells were the only type of mast cells seen in all specimens analysed and in each case were more numerous in superficial compared to deep regions of dermis. The concentration (mean +/- s.d.) of mast cells in the superficial dermis of mastocytosis lesions (40 985 +/- 21 772 mast cells/mm3) was significantly increased over that in corresponding areas of non-lesional skin from subjects with mastocytosis (7178 +/- 3607 mast cells/mm3), skin from subjects with idiopathic anaphylaxis or flushing episodes (6974 +/- 3873 mast cells/mm3) and normal skin (7347 +/- 2973 mast cells/mm3). The exclusive presence of MCTC cells in skin lesions of mastocytosis which are characterized by non-malignant hyperplasia of mast cells suggests involvement of local tissue factors in mast cell recruitment and differentiation.

Biopsy↗
PubMed1995

Proliferative activity of mast cells in allergic nasal mucosa.

The proliferative activity of mast cells in the nasal mucosae of allergic (n = 14) and non-allergic (n = 18) rhinopathic patients was studied by a sequential double immunohistochemistry using anti-proliferating cell nuclear antigen (PCNA) and anti-tryptase antibodies. Two hundred to 300 tryptase-positive cells (mast cells) were studied in each allergic nasal epithelium. In case of non-allergic nasal mucosa, only a few mast cells existed in the epithelial layer. The total number of mast cells which we could detect in all patients was 168 cells. One of these cells contained PCNA. Three hundred to 500 mast cells were studied in each subepithelial layer and deep layer of lamina propria of both diseases. PCNA-positive mast cells were observed in the nasal epithelia of 10 allergic patients. In the subepithelial layer, PCNA-positive mast cells were observed eight allergic patients and four non-allergic patients, respectively. In the deep lamina propria, PCNA-positive mast cells were observed in a few patients with both diseases. The percentage of PCNA-positive mast cells of all mast cells each area ranged from 0 to 1.7%. The incidence of PCNA-positive mast cells was statistically higher in the allergic epithelium and subepithelial layer than in the deep layer of lamina propria. Moreover, that of PCNA-positive mast cells in the subepithelial layer was higher in allergic than in non-allergic nasal mucosa. Our results suggest that mast cell proliferation may contribute to the number of mast cells in the nasal epithelium and subepithelial layer of allergic patients.

Adolescent↗
PubMed2005

Diagnosis of Hymenoptera venom allergy.

The purpose of diagnostic procedure is to classify a sting reaction by history, identify the underlying pathogenetic mechanism, and identify the offending insect. Diagnosis of Hymenoptera venom allergy thus forms the basis for the treatment. In the central and northern Europe vespid (mainly Vespula spp.) and honeybee stings are the most prevalent, whereas in the Mediterranean area stings from Polistes and Vespula are more frequent than honeybee stings; bumblebee stings are rare throughout Europe and more of an occupational hazard. Several major allergens, usually glycoproteins with a molecular weight of 10-50 kDa, have been identified in venoms of bees, vespids. and ants. The sequences and structures of the majority of venom allergens have been determined and several have been expressed in recombinant form. A particular problem in the field of cross-reactivity are specific immunoglobulin E (IgE) antibodies directed against carbohydrate epitopes, which may induce multiple positive test results (skin test, in vitro tests) of still unknown clinical significance. Venom hypersensitivity may be mediated by immunologic mechanisms (IgE-mediated or non-IgE-mediated venom allergy) but also by nonimmunologic mechanisms. Reactions to Hymenoptera stings are classified into normal local reactions, large local reactions, systemic toxic reactions, systemic anaphylactic reactions, and unusual reactions. For most venom-allergic patients an anaphylactic reaction after a sting is very traumatic event, resulting in an altered health-related quality of life. Risk factors influencing the outcome of an anaphylactic reaction include the time interval between stings, the number of stings, the severity of the preceding reaction, age, cardiovascular diseases and drug intake, insect type, elevated serum tryptase, and mastocytosis. Diagnostic tests should be carried out in all patients with a history of a systemic sting reaction to detect sensitization. They are not recommended in subjects with a history of large local reaction or no history of a systemic reaction. Testing comprises skin tests with Hymenoptera venoms and analysis of the serum for Hymenoptera venom-specific IgE. Stepwise skin testing with incremental venom concentrations is recommended. If diagnostic tests are negative they should be repeated several weeks later. Serum tryptase should be analyzed in patients with a history of a severe sting reaction.

Allergens↗
PubMed2004

The distribution of mast cells in the human area postrema.

The topography and phenotype of mast cells in the human area postrema, together with correlation between mast-cell density and microvessel density (MVD), were analysed in 16 brains. Transverse serial sections of formalin-fixed, paraffin-embedded brainstems were stained with toluidine blue and alcian blue/safranin stainings, and with anti-tryptase and anti-CD31 monoclonal antibodies. The mean (+/- SD) numbers of mast cells per section were 1.3 +/- 0.8 and 1.2 +/- 0.7 with toluidine blue and alcian blue/safranin, respectively, whereas anti-tryptase monoclonal antibody showed a mean of 5.1 +/- 2.4 cells. Mast cells were alcian blue- and safranin-positive in 56%, because of the coexistence of low-sulphated (blue-staining) and high-sulphated (red-staining) granules. No significant linear correlation between mast-cell density (4.9 mm(-2)) and MVD (114.5 mm(-2)) was found (r(2) = 0.19, P = 0.09). Mast cells were frequently located close to blood vessels (55%) (33% to venules, 22% to arterioles), indicating that their products play a role in the regulation of blood flow and in vessel permeability in the area postrema. Mast cells were located subependymally in 44% and close to the dorsal aspect of the nucleus of the tractus solitarius in 31%, suggesting a subregional distribution.

Alcian Blue↗
PubMed2004

Mast cells--a role in periodontal diseases?

OBJECTIVES: Limited attention has been given to the role mast cells may play in periodontal diseases. BACKGROUND: Mast cells are indeed found abundantly below and within several types of mucosal epithelia. On the basis of their proteinase content, mast cells are divided into connective tissue (CT) and mucosal phenotypes. The CT phenotype contains both tryptase and chymase (MC(TC)), while the mucosal phenotype contains only tryptase (MC(T)). The in vivo significance of different mast cell phenotypes has not yet been fully established. Mast cells are able to phagocytose, process and present antigens as effectively as macrophages. RESULTS: Recently mast cells were found in high numbers in chronically inflamed gingival tissue taken from patients with chronic marginal periodontitis (CMP). The number of mast cells was found to be even higher in HIV(+) patients with CMP. Furthermore, mast cells also express strongly matrix metalloproteinases (MMPs), which are key enzymes in degradation of gingival extracellular matrix. Mast cells may release preformed cytokines directing local innate and adaptive immune responses. The present review will focus on possible roles for mast cells in periodontal diseases. CONCLUSIONS: We certainly feel that this is a key cell in inflamed periodontal tissue and its role in periodontitis needs to be revisited.

Cytokines↗
PubMed1996

Immune-associated cells in basal cell carcinomas of skin.

Increased numbers of mast cells (MCs) and lymphocytes infiltrating in basal cell carcinomas (BCCs) have been observed. The presence of these infiltrating cells has been considered a sign of an immunologic anti-tumor response in the host, but the relationship of these two cell populations has not been examined. To elucidate this possible relationship, 30 non-ulcerated BCCs were analyzed. Frozen sections of the tumors were stained with monoclonal antibodies for Langerhans' cells, lymphocyte subsets and natural killer cells. Fluorescein isothiocynate (FITC)-avidin as well as anti-tryptase and anti-CD45RO monoclonal antibodies were used on formalin-fixed, paraffin-embedded sections for mast cell and T cell identification, respectively. B cells and natural killer cells were rarely observed in these tumors. MCs and T cells were quantified by direct enumeration and expressed as number of cells per high power field (hpf). FITC-avidin and anti-tryptase antibodies were equivalent in their ability to identify MCs. MC content in BCCs ranged from 1.0 to 31 cells/hpf. The number of T cells ranged from 0 to 50 cells/hpf with helper/suppressor cell ratios of 0.2 to 10. There was no correlation between helper/suppressor ratios and mast cell numbers; however, an inverse relationship was observed between the numbers of T cells and the number of mast cells in these tumors. These studies indicate that T cells and MCs are the primary immune cell populations responding to BCCs, and that decreased numbers of T cells are associated with more aggressive tumors.

Basal Cell Carcinoma↗
PubMed1999

Mast cells and their mediators in cutaneous wound healing--active participants or innocent bystanders?

Mast cells are traditionally viewed as effector cells of immediate type hypersensitivity reactions. There is, however, a growing body of evidence that the cells might play an important role in the maintenance of tissue homeostasis and repair. We here present our own data and those from the literature elucidating the possible role of mast cells during wound healing. Studies on the fate of mast cells in scars of varying ages suggest that these cells degranulate during wounding, with a marked decrease of chymase-positive cells, although the total number of cells does not decrease, based on SCF-receptor staining. Mast cells contain a plethora of preformed mediators like heparin, histamine, tryptase, chymase, VEGF and TNF-alpha which, on release during the initial stages of wound healing, affect bleeding and subsequent coagulation and acute inflammation. Various additional vasoactive and chemotactic, rapidly generated mediators (C3a, C5a, LTB4, LTC4, PAF) will contribute to these processes, whereas mast cell-derived proinflammatory and growth promoting peptide mediators (VEGF, FGF-2, PDGF, TGF-beta, NGF, IL-4, IL-8) contribute to neoangiogenesis, fibrinogenesis or re-epithelization during the repair process. The increasing number of tryptase-positive mast cells in older scars suggest that these cells continue to be exposed to specific chemotactic, growth- and differentiation-promoting factors throughout the process of tissue remodelling. All these data indicate that mast cells contribute in a major way to wound healing. their role as potential initiators of or as contributors to this process, compared to other cell types, will however have to be further elucidated.

Humans↗
PubMed1999

Alterations in ganglioside expression during the differentiation of human mast cells.

Gangliosides are physiological components of the outer cell membrane. In the present study, the role of ganglioside expression during differentiation of human mast cells was evaluated. After 11 days of culture in medium known to induce mast cell differentiation, 70% of peripheral blood mononuclear cells (PBMC) showed positive staining for the high affinity IgE receptor and tryptase on immunocytochemistry and an associated 20-fold increase of ganglioside GM3 expression. Furthermore, exogenous addition of GM3 during cultivation of PBMC in medium containing low levels of growth factors induced an increase of mast cell specific tryptase. The association of ganglioside expression with mast cell differentiation was confirmed by experiments with the human mast cell line HMC-1. FcepsilonRI-positive cultured cells enriched with immunobeads exhibited a 3-fold higher expression of GM3, compared to FcepsilonRI negative HMC-1 cells. Furthermore, measurable amounts of the gangliosides GM2, GM1 and GD1a were found only in the FcepsilonRI positive cells. A corresponding transient increase of mRNA for GalNAcT, the key enzyme in the production of these latter gangliosides, could be detected preceding the expression of these gangliosides and the FcepsilonRI by RT-PCR. Taken together, these data point to a functional role of gangliosides in the differentiation of human mast cells.

Basophils↗
PubMed1999

Decidual mast cells might be involved in the onset of human first-trimester abortion.

PROBLEM: The aim of the present study was to identify the role of mast cells and substance P (SP)-containing nerve fibers in human decidua in normal and pathological pregnancies. METHOD OF STUDY: We collected decidua from women undergoing termination of normal pregnancies and from abortions. The presence of mast cells and SP was detected by immunohistochemistry. RESULTS: We observed a sparse distribution of mast cells in the normal pregnancies (36.7 tryptase+ mast cells/mm2 decidua). In the decidua from abortion, we found a dramatic increase in the number of mast cells (448.7 and 469.2 tryptase+ mast cells/mm2 decidua in primary and secondary abortions, respectively). In addition, we observed an increase of SP-positive nerve fibers in the decidua of abortions. CONCLUSIONS: Our data suggest that decidual mast cells may play an important role in the onset of abortion, due to the production of cytokines, such as tumor necrosis factor-alpha.

Abortion, Induced↗
PubMed1991

The role of basophils in asthma.

The characteristics of the acute and late human response to antigen in the upper and lower airways and in the skin is summarized in TABLE 2. This table makes it clear that while mast cells are responsible for the mediator release of the acute phase, eosinophils and basophils are the cells involved in the mediator release which occurs during the experimental late phase reaction. The pattern of mediators observed during the acute response is quite characteristic of the mast cell. Thus, in the nose, skin, and lungs, the acute response is characterized by significant increases in histamine, PGD2, tryptase, and sometimes LTC4. In the late phase reaction, the pattern of mediator release is characteristic of basophils and eosinophils, and includes histamine, LTC4 (where measurable), and eosinophil-derived proteins, without PGD2 or tryptase. Basophils have been identified at appropriate time-points in each model using morphologic and phenotypic criteria, and their numbers relate to the histamine levels. Finally, treatment with glucocorticosteroids, the most potent drugs available for treating chronic allergic inflammation, obliterates the late phase reaction and decreases both mediator release and the infiltration of eosinophils and basophils. Chronic allergic inflammation is now taken by both the pulmonary and immunologic community as a hallmark of asthma, and it can be stated without equivocation that the basophils are responsible for the mediator release observed in that response.

Asthma↗
PubMed1994

Differentiation of human mast cells from bone-marrow and cord-blood progenitor cells by factors produced by a mouse stromal cell line.

Human bone-marrow or cord-blood progenitors (i.e., CD34+ cells) are easily purified by immunological methods and can be cultured on normal human-bone-marrow stromal cells for limited periods of time. Under these culture conditions, the number of progenitors declines in a few weeks and these cells disappear completely in less than 8 weeks. This fact suggests that this culture system is deprived of growth factor(s) able to support the self-renewal of stem cells. We have developed the culture of immunomagnetically purified human-bone-marrow- or cord-blood-derived CD34+ cells on a supportive mouse lipoblastic stromal cell line, MS-5. The long-term survival of clonogenic cells was analyzed in these cultures and compared with the results obtained by culture on human-bone-marrow stromal cells. The results demonstrated that only coculture of CD34+ cells on MS-5 layers allows the survival of clonogenic progenitors for at least 12 weeks. Cytospin smears were regularly performed and cell morphology was examined after classical staining methods (i.e., M.G.G. and toluidine blue staining). Histologic analysis demonstrated the growth of mast-cell-like metachromatic cells after the second week of incubation on MS-5 layer. The highest percentage of these cells was observed after 8 weeks, and averaged about 30 percent for cord-blood cells and 70 percent for bone-marrow cells. To further confirm the nature of the metachromatic cells obtained under this culture condition, immunohistochemical staining of tryptase was performed on the same samples. The results demonstrated similar percentages of tryptase+ cells and of metachromatic elements. Measurement of cellular histamine demonstrated that culture of CD34+ cells on MS-5 monolayers induced the formation and increase of this mediator. To determine whether the contact between MS-5 layers and CD34+ cells was an absolute requirement for the development of mast cells, CD34+ cells were cultured in the presence of MS-5 conditioned medium. This condition allowed the development of similar percentage of mast cells when compared with the coculture experiments, indicating that a soluble factor was involved in mast cell differentiation. Whatever the soluble factor(s) responsible for this mast cell growth activity, our culture system allows us to obtain significant amounts of highly enriched normal human mast cell populations useful for further studies on the reactivity of this cell subset.

Animals↗
PubMed2004

Protease-activated receptor-2-mediated proliferation and collagen production of rat pancreatic stellate cells.

Activated pancreatic stellate cells (PSCs) play a pivotal role in the pathogenesis of pancreatic inflammation and fibrosis. Trypsin and tryptase, which are agonists for protease-activated receptor-2 (PAR-2), are involved in the pathogenesis of pancreatitis. Here, we examined whether PSCs expressed PAR-2 and its agonists affect the cell functions of PSCs. PSCs were isolated from rat pancreas tissue. Expression of PAR-2 was examined by Western blotting and reverse transcription-polymerase chain reaction. Trypsin, activating peptide (SLIGRL-NH(2), corresponding to the PAR-2 tethered ligand), and tryptase were tested for their ability to affect proliferation, chemokine production, and collagen synthesis in culture-activated PSCs. Activation of mitogen-activated protein (MAP) kinases was assessed by Western blotting using antiphosphospecific antibodies. The effect of PAR-2 agonists on the activation of freshly isolated PSCs in culture was also examined. PAR-2 expression was observed in culture-activated PSCs, whereas it was undetectable in freshly isolated PSCs. PAR-2 agonists activated activator protein-1 and MAP kinases (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAP kinase) but not nuclear factor kappaB. PAR-2 agonists induced proliferation of PSCs through the activation of extracellular signal-regulated kinase. PAR-2 agonists increased collagen synthesis through the activation of c-Jun N-terminal kinase and p38 MAP kinase. PAR-2 agonists did not induce the production of monocyte chemoattractant protein-1 and cytokine-induced neutrophil chemoattractant-1 or initiate the transformation of freshly isolated PSCs in culture. Taken together, our results suggest a role of PAR-2 in the sustenance of pancreatic fibrosis through the increased proliferation and collagen production in PSCs.

Animals↗
PubMed2002

Proteinase-activated receptor (PAR)-1 and -2 agonists induce mediator release from mast cells by pathways distinct from PAR-1 and PAR-2.

Because thrombin-induced inflammation is partially mast cell-dependent and involves proteinase-activated receptors (PARs), we hypothesized that mast cells express PAR and can be stimulated with PAR-activating peptides (PAR-AP). We demonstrated that rat peritoneal mast cells expressed PAR-1 and PAR-2 mRNA, and that PAR-2AP (tc-LIGRLO-NH(2), 1 microm) induced 64.2 +/- 4.4% specific beta-hexosaminidase release from peritoneal mast cells, whereas another PAR-2AP (SLIGRL-NH(2), 10 microM), trypsin (40 U/ml), and mast cell tryptase (1.5 microg/ml) did not. PAR-1AP (ApfFRChaCitY-NH(2), 10 microM) (Cit) induced 11.7 +/- 3.7% specific beta-hexosaminidase release, whereas another PAR-1AP (TFLLR-NH(2), 40 microM) and human thrombin (10 U/ml) did not. PAR-AP, tc-LIGRLO-NH(2), and Cit increased the free intracellular Ca(2+) concentration, whereas trypsin, tryptase, thrombin, and other PAR-APs did not. Desensitization of Ca(2+) flux with different agonists suggests that although tc-LIGRLO-NH(2), Cit, and compound 48/80 have similar mechanisms of action, tc-LIGRLO-NH(2) also activates mast cells by a mechanism distinct from that of 48/80. Using benzalkonium chloride, which antagonizes the actions of 48/80 by competing for the same G(i) protein, we determined that benzalkonium chloride suppressed tc-LIGRLO-NH(2)-mediated (0.1 microM) beta-hexosaminidase release by 62%. Moreover, removal of sialic acid from peritoneal mast cells, using neuraminidase (2 U/ml), inhibited Cit- (10 microM, 52%) and tc-LIGRLO-NH(2) (0.5 microM, 29%)-mediated beta-hexosaminidase release. Thus, tc-LIGRLO-NH(2) and Cit have at least partially similar mechanisms of action as 48/80. PAR-AP may therefore activate mast cells via multiple mechanisms that are distinct from those of classical PAR-1 and PAR-2. The responsiveness of mast cells to PAR-AP via a non-PAR-1/non-PAR-2 mechanism complicates the interpretation of in vivo studies using these peptides.

Animals↗
PubMed2005

Macrophages overloaded with tissue debris in Wegener's granulomatosis.

OBJECTIVES: To analyse some scavenging related molecules in Wegener's granulomatosis (WG) macrophages. METHODS: Immunohistochemical staining of lung, nasopharynx, and skin for macrophage markers related to scavenging (macrophage scavenger receptor MARCO, collagenase-1 and gelatinase-B), formation of multinuclear foreign body giant cells (ADAM 9/meltrin-gamma and ADAM 12/meltrin-alpha), and cell debris derived from neutrophils, endothelial cells and mast cells (specific granule protein 28 (SGP28), von Willebrand factor (vWF) and mast cell tryptase, respectively). TechMate staining robot and biotin-streptavidin protocol were used. RESULTS: Some macrophages were activated and expressed collagenase-1 and gelatinase-B. Approximately 5% of macrophages expressed scavenger receptor, whereas 20-30% were meltrin positive. Interstitial and granuloma associated macrophages and giant cells contained partly undigested, immunoreactive SGP28-, vWF- and tryptase-positive cell rests and collagenous matrix. Lymphocytic follicles with germinal centres were found in the same areas. CONCLUSION: In WG tissue lesions macrophage and giant cells seem to be overwhelmed by the bulk to be scavenged. Despite cellular activation and continuing maturation to professional scavenger receptor (MARCO) and meltrin positive multinuclear giant cells combined with an organisation into granulomas, macrophages still contain partially undigested cell and tissue rests. This necrotic and damaged self may be the driving force for the formation of giant cell ("foreign body") granulomas. This, together with the local formation of secondary lymphatic follicles (with germinal centres), indicates active local antigen processing and presentation.

Collagenases↗
PubMed2006

Morphological and quantitative assessment of mast cells in rheumatoid arthritis associated non-specific interstitial pneumonia and usual interstitial pneumonia.

BACKGROUND: The role of mast cells in extra-articular manifestations of rheumatoid arthritis (RA) has not been studied so far. OBJECTIVE: To characterise and quantify mast cells in RA associated interstitial pneumonia (IP) by an immunohistological study. METHODS: Lung biopsy specimens from 15 patients with RA associated IP, 12 patients with idiopathic IP, and 5 control patients were stained with antibodies directed against tryptase (mast cell marker). Morphological characterisation of stained specimens was carried out and staining was quantified by computer assisted image analysis. RESULTS: Tryptase staining showed the marked presence of mast cells in idiopathic IP and in RA associated IP. A significant difference in stained tissue area was found between RA associated IP (2.6%, IQR 2.0-3.2%, p = 0.015) and idiopathic IP (3.1%, IQR 1.8-3.7%, p = 0.003) compared with control tissue specimens (1.0%, IQR 0.7-1.5%). The extent of mast cell infiltration correlated well and inversely with pulmonary function variables. CONCLUSIONS: Mast cell infiltrates are present in RA associated IP and idiopathic IP. The observed correlation of pulmonary function and mast cell numbers would be consistent with the proposed role of mast cell mediators in the promotion of fibrogenesis. The findings provide a rationale for studying functional aspects of mast cell involvement in the pathogenesis of RA associated lung disease.

Aged↗
PubMed2004

Nebulised salbutamol administered during sputum induction improves bronchoprotection in patients with asthma.

BACKGROUND: Inhalation of hypertonic or even isotonic saline during sputum induction may cause bronchospasm in susceptible patients with asthma, despite premedication with 400 microg inhaled salbutamol delivered by pressurised metered dose inhaler (pMDI). The bronchoprotection afforded by additional inhaled salbutamol administered through the ultrasonic nebuliser during sputum induction was investigated. METHODS: Twenty patients with moderate to severe asthma underwent sputum induction by inhaling saline 4.5% (or 0.9% if post-bronchodilation forced expiratory volume in 1 second (FEV1) <65% predicted) for 10 minutes according to two protocols given 1 week apart in random order. At visit A the patients received 400 microg salbutamol administered through a pMDI+spacer 20 minutes before induction while at visit B the premedication was supplemented by 1500 microg nebulised salbutamol inhaled throughout the induction procedure. Both the investigator and the patients were blind to the nebulised solution used. FEV1 was recorded during sputum induction at 1, 3, 5, and 10 minutes. Sputum cell counts and histamine, tryptase and albumin levels in the supernatants were determined. RESULTS: The mean (SE) maximal reduction in FEV1 over the 10 minute period of sputum induction was 11.7 (2.8)% at visit A, which was significantly greater than at visit B (2.6 (1.2)%; mean difference 9% (95% CI 2.7 to 15.4), p<0.01). Total and differential sputum cell counts as well as albumin, tryptase, and histamine levels did not differ between the two visits. CONCLUSION: The addition of inhaled salbutamol through an ultrasonic nebuliser markedly improves bronchoprotection against saline induced bronchoconstriction in patients with moderate to severe asthma undergoing sputum induction without affecting cell counts and inflammatory markers.

Administration, Inhalation↗
PubMed1996

Effect of endobronchial aspirin challenge on inflammatory cells in bronchial biopsy samples from aspirin-sensitive asthmatic subjects.

BACKGROUND: The aspirin-induced bronchoconstriction in patients with aspirin-sensitive asthma is caused by cysteinyl leukotriene release. The cellular source of the leukotrienes is unknown. The inflammatory cell infiltrate in bronchial biopsy samples from seven aspirin-sensitive asthmatic (ASA) subjects and eight non-ASA subjects before and after local challenge with lysine aspirin was therefore examined. METHODS: Using flexible bronchoscopy, airway mucosal biopsy samples were taken and lysine aspirin solution was placed directly onto a carina of the contralateral lung. Twenty minutes later a second series of biopsy samples was taken from the site of the local endobronchial lysine aspirin challenge. The biopsy samples were double immunostained with a rabbit polyclonal antibody to the enzyme 5-lipoxygenase and monoclonal antibodies to mast cells (AA1), neutrophils (NP57), macrophages (EBM11), T lymphocytes (anti-CD3), and total (BMK13) and activated eosinophils (EG2). RESULTS: A decrease in both absolute mast cell numbers staining with mast cell tryptase (AA1) and the percentage of mast cells co-immunostaining with 5-lipoxygenase was seen in the ASA patients after lysine aspirin challenge compared with the non-ASA control group. There was also an increase in the numbers of activated eosinophils (EG2) in the ASA subjects compared with the non-ASA group. No changes were observed in the total numbers of macrophages (EBM11), neutrophils (NP57), total eosinophils (BMK13), and T lymphocytes (anti-CD3) after challenge with lysine aspirin. CONCLUSIONS: The decrease in numbers of mast cells staining for tryptase and the increase in activated eosinophils after endobronchial challenge with lysine aspirin may represent degranulation of these cell types, and may be an early event associated with aspirin-sensitive reactions in ASA subjects.

Administration, Topical↗
PubMed1997

Nasal responsiveness to allergen and histamine in patients with perennial rhinitis with and without a late phase response.

BACKGROUND: In the lower airways an association has been found between early phase reaction (EPR), late phase reaction (LPR), and bronchial hyperreactivity. However, this association has not been shown for the upper airways in nasal pollen challenge studies. A study was undertaken to determine whether the EPR, LPR, and nasal hyperreactivity are related in perennial allergic rhinitis. METHODS: Twenty four patients with rhinitis who were allergic to house dust mite (HDM) were challenged with HDM extract. The nasal response was monitored by symptom scores and nasal lavages for up to 9.5 hours after challenge and concentrations of albumin, tryptase, and eosinophil cationic protein (ECP) in the lavage fluid were measured. Thirteen patients (defined as dual responders) had increased symptom scores between 3.5 and 9.5 hours compared with the baseline score. The other 11 patients (defined as early responders) showed an isolated EPR only. Nasal hyperreactivity was determined by nasal histamine challenge 24 hours later. RESULTS: Dual responders showed a significantly higher symptom score, albumin influx, and tryptase release during the EPR. During the late phase (3.5-9.5 hours) albumin influx was significantly increased at most time points and ECP release was significantly higher at 9.5 hours in the dual responder group. Dual responders showed a significantly stronger response to all doses of histamine. The area under the curve (AUC) of symptom scores during EPR and LPR and the AUC of the histamine dose response were significantly correlated (EPR-LPR: r = 0.49, p < 0.01; EPR-histamine: r = 0.75, p < 0.001; LPR-histamine: r = 0.66, p < 0.001). CONCLUSIONS: In patients with perennial allergic rhinitis the nasal responses to allergen and histamine are associated. Dual responders have an increased EPR, increased levels of mediators, and increased allergen-induced hyperreactivity.

Adult↗