Basophil's secrets revealed by flow cytometry.
Explore the source record for details and available documents.
Basophils↗
Biomedical subjects
M Triggiani
Publications and source records attributed to M Triggiani.
Differential modulation of mediator release from human basophils and mast cells by mizolastine.
BACKGROUND: Basophils and mast cells play a major role in the pathogenesis of allergic disorders by releasing several proinflammatory mediators. Some histamine H1 receptor antagonists exert anti-inflammatory activities by modulating mediator release from basophils and mast cells. OBJECTIVE: To study the in vitro effects of mizolastine, an H1 receptor antagonist, on the release of eicosanoids, histamine and IL-4 from human basophils and lung mast cells. METHODS AND RESULTS: Mizolastine (10(-7)-10(-5) M) concentration-dependently inhibited the release of cysteinyl leukotriene C4 from anti-IgE-stimulated basophils (IC(50): 3.85+/-0.28 microM) and mast cells (IC(50): 3.92+/-0.41 microM). The same concentrations of mizolastine did not affect anti-IgE-induced prostaglandin D2 release from lung mast cells. In contrast, mizolastine enhanced up to 80% IgE-mediated histamine release (EC(50): 4.63+/-0.14 microM) from basophils, but not from mast cells and it significantly potentiated IL-4 release from basophils induced by anti-IgE. Mizolastine did not affect histamine release from basophils induced by formyl peptide, whereas it inhibited cysteinyl leukotriene C4 release (IC(50): 1.86+/-0.24 microM). Blockade of cytosolic phospholipase A2 and arachidonic acid mobilization by pyrrolidine-1 did not alter the effect of mizolastine on histamine release from basophils, thereby excluding accumulation of arachidonic acid metabolic intermediates as the cause of this effect. Mizolastine did not influence anti-IgE-induced activation of extracellular signal-regulated kinase-1 and -2 (ERK-1 and -2) in human basophils. CONCLUSIONS: Mizolastine efficiently inhibits LTC4 synthesis in human basophils and mast cells presumably by interfering with 5-lipoxygenase. In contrast, it enhances histamine and IL-4 release only from anti-IgE-stimulated basophils. Therefore, mizolastine differentially regulates the production of mediators from basophils and mast cells in a cell- and stimulus-specific fashion.
Antibodies, Anti-Idiotypic↗
Diagnosis of complete mainstem bronchus avulsion by 3-dimensional spiral CT scan of the chest.
Tracheobronchial injury (TBI) after blunt trauma of the chest is a rare life-threatening entity that can be successfully managed by surgery if there is an early diagnosis. A 18-year-old man was injured in a motocycle accident. Three consecutive flexible bronchoscopies risulted negative for tracheo-bronchial lesions. Then, the patient was submitted to a spiral CT-scan of the chest with 3-dimensional reconstruction of the tracheobronchial tree that showed a rupture of the right main bronchus from the trachea. The lesion was successfully treated by surgery. Bronchoscopic findings in TBI may be unclear also for an experienced thoracic surgeon.
Accidents, Traffic↗
Severe oral symptoms after the use of an oral solution containing ketoprofen in two NSAIDs-sensitive patients.
Cutaneous application of the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen has been reported to induce contact dermatitis. However, there is no report of intraoral symptoms after the use of solutions containing this drug. In this report we describe two cases of severe intraoral symptoms after the use of a gargle containing ketoprofen in two patients with NSAIDs hypersensitivity. The patients underwent diagnostic procedures 6 months after the episodes of intraoral symptoms. Procedures included skin prick test for inhalant and food allergens, and total- and specific-IgE determinations to evaluate the presence of atopy. A single-blind, placebo-controlled challenge with different dilutions (1/1000, 1/100, 1/10, and 1/1) of ketoprofen oral solution was carried out by a modified version of a standardized protocol. We used the same commercial solution without the drug as placebo. Diagnostic procedures failed to demonstrate allergic sensitization to the common inhalant and food allergens. Both patients experienced a slight intraoral itching and edema of the lips a few minutes after the intraoral use of 1/100 dilution of active drug. Our cases suggest that the contact of an oral solution containing ketoprofen with oral mucosa may induce locally severe oral manifestations. Patients with NSAIDs sensitivity should be warned on the potential risk of using an oral solution containing this class of drugs.
Administration, Oral↗
Pharmacological modulation of human mast cells and basophils.
Explore the source record for details and available documents.
Anti-Inflammatory Agents, Non-Steroidal↗
A multicenter evaluation of the CARLA system for the measurement of specific IgE antibodies vs. other different methods and skin prick tests.
The evaluation of specific IgE by using appropriate immunoassays represents a useful alternative diagnostic procedure where skin prick tests (SPTs) are not conclusive in clarifying the etiological role of suspected allergens. This study compares the results of the evaluation of specific IgE by using the CARLA system vs. other commercially available immunoassays (CAP system, Ala-STAT Medical system, ALLERgen IFCI Clone System) carried out on the same blood samples obtained from allergic/SPTs negative patients and vs. SPTs. We evaluated serum specific IgE produced against five selected allergens (Dermatophagoides pteronyssinus, Olea europaea, Parietaria judaica, Lolium perenne and Phleum pratense) by using these immunoassays and the correlations between the results of SPTs and IgE evaluations. We demonstrated a good correlation between these last parameters including a high degree of sensitivity and specificity. The reproducibility of the CARLA system was very high by comparing the results obtained by two different laboratories. The results of the CARLA system were well correlated to those of other well-known immunoassays such as CAP system and Ala STAT system. In conclusion, the CARLA system represents an efficient and reliable immunoassay for the evaluation of serum specific IgE.
Adolescent↗
Histamine induces exocytosis and IL-6 production from human lung macrophages through interaction with H1 receptors.
Increasing evidence suggests that a continuous release of histamine from mast cells occurs in the airways of asthmatic patients and that histamine may modulate functions of other inflammatory cells such as macrophages. In the present study histamine (10(-9)-10(-6) M) increased in a concentration-dependent fashion the basal release of beta-glucuronidase (EC(50) = 8.2 +/- 3.5 x 10(-9) M) and IL-6 (EC(50) = 9.3 +/- 2.9 x 10(-8) M) from human lung macrophages. Enhancement of beta-glucuronidase release induced by histamine was evident after 30 min and peaked at 90 min, whereas that of IL-6 required 2-6 h of incubation. These effects were reproduced by the H(1) agonist (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)heptane carboxamide but not by the H(2) agonist dimaprit. Furthermore, histamine induced a concentration-dependent increase of intracellular Ca(2+) concentrations ([Ca(2+)](i)) that followed three types of response, one characterized by a rapid increase, a second in which [Ca(2+)](i) displays a slow but progressive increase, and a third characterized by an oscillatory pattern. Histamine-induced beta-glucuronidase and IL-6 release and [Ca(2+)](i) elevation were inhibited by the selective H(1) antagonist fexofenadine (10(-7)-10(-4) M), but not by the H(2) antagonist ranitidine. Inhibition of histamine-induced beta-glucuronidase and IL-6 release by fexofenadine was concentration dependent and displayed the characteristics of a competitive antagonism (K(d) = 89 nM). These data demonstrate that histamine induces exocytosis and IL-6 production from human macrophages by activating H(1) receptor and by increasing [Ca(2+)](i) and they suggest that histamine may play a relevant role in the long-term sustainment of allergic inflammation in the airways.
Calcium↗
Chordal plication and free edge remodeling for mitral anterior leaflet prolapse repair: 8-year follow-up.
BACKGROUND: Chordal suture plication and free edge remodeling represent a personal technique for the repair of anterior leaflet prolapse. We report the results of an 8-year experience. METHODS: Sixty-one patients with degenerative mitral regurgitation caused by prolapse of the anterior leaflet (11) or both leaflets (50) underwent anterior leaflet prolapse repair. Twenty patients who had associated cardiac procedures are included. RESULTS: There were two perioperative deaths. Postoperative mitral regurgitation fell to 0.4 +/- 0.7 versus 3.7 +/- 0.4 preoperative (p < 0.0001). Mean follow-up was 40.5 months. There were 3 late deaths and 3 mitral reoperations (1 of 3 repairs, 2 of 3 replacements). Thromboembolism and endocarditis occurred in 1 patient each. Actuarial overall survival, freedom from cardiac death, and freedom from mitral reoperation at 92 months were 85.1% +/- 7.9%, 88.9% +/- 7.7%, and 94.6% +/- 3.0%, respectively. CONCLUSIONS: Our technique of anterior leaflet prolapse repair appears effective, safe, and durable at mid- to long-term follow-up, and may be used in the presence of extensive disease of both leaflets.
Adult↗
Treatment of mastocytosis: pharmacologic basis and current concepts.
Mastocytosis is a rare, heterogeneous disorder characterized by a marked increase in mast cell density in various tissues. Mast cells from different human tissues are heterogeneous. So far, there is no cure for systemic mastocytosis. Conventional therapy is based on agents that antagonize mediators released from mast cells, drugs that inhibit the release of mediators and agents that modulate mast cell proliferation. This pharmacologic approach is satisfactory in the majority of patients with indolent mastocytosis. At the beginning of the new millennium, the therapy of severe forms of aggressive mastocytosis remains a challenge for students of this intriguing disorder.
Adenylyl Cyclases↗
Human mast cells and basophils in HIV-1 infection.
Mast cells and basophils (FcvarepsilonRI(+) cells) are classically involved in allergic disorders. HIV-1 glycoprotein gp120 acts as a viral superantigen by interacting with the heavy chain, variable 3 (V(H)3) region of IgE to induce cytokine release from FcvarepsilonRI(+) cells. The chemokine receptors CCR3 and CXCR4, co-receptors for HIV-1, are expressed by FcvarepsilonRI(+) cells. Via its interaction with CCR3, HIV-1 transactivation (Tat) protein is a potent chemoattractant for FcvarepsilonRI(+) cells. Incubation of basophils with Tat protein upregulates the surface expression of the CCR3 receptor. There is some evidence that human FcvarepsilonRI(+) cells could be infected in vitro by M-tropic HIV-1 strains.
Basophils↗
Role of human FcepsilonRI+ cells in HIV-1 infection.
Enhanced serum IgE levels in adults and children with HIV-1 infection could be a marker of poor prognosis. HIV-1 infection is believed to involve a switch toward a "TH2-like" cytokine pattern. HIV-1 gp120 from different clades is a potent stimulus for histamine release from human basophils and mast cells. Gp120 also induces IL-4 and IL-13 synthesis from basophils. It functions as a viral superantigen by interacting with the VH3 region of IgE to induce mediator release from human FcepsilonRI+ cells. The chemokine receptor CCR3, which binds the chemokines eotaxin and RANTES, is expressed by basophils and lung mast cells. By interacting with the CCR3 receptor on FcepsilonRI+ cells, HIV-1 Tat protein is a potent chemoattractant for basophils and lung mast cells. Tat protein also induces IL-4 and IL-13 release from basophils. Incubation of basophils with Tat protein upregulates the surface expression of the CCR3 receptor, a co-receptor of HIV-1 infection. Extracellular Tat affects the directional migration of human FcepsilonRI+ cells, CCR3 expression and TH2 cytokines release. We have shown that HIV-1 proteins gp120 and Tat trigger the release of cytokines critical for TH2 polarization from FcepsilonRI+ cells through two distinct mechanisms. In addition, Tat upregulates the beta-chemokine receptor CCR3, making FcepsilonRI+ cells more susceptible to infection with CCR3 tropic HIV-1 isolates.
Antibodies, Monoclonal↗
Are mast cells MASTers in HIV-1 infection?
HIV-1 gp120 interacts with IgE V(H)3(+) on the surface of human basophils and mast cells (Fc epsilon RI(+) cells), acting as a viral immunoglobulin superantigen. gp120 from different clades induces mediator release from Fc epsilon RI(+) cells. gp120 also induces IL-4 and IL-13 synthesis in human basophils. The chemokine receptors CCR3 and CXCR4, which are coreceptors of HIV-1 infection, are expressed by human Fc epsilon RI(+) cells. HIV-1 Tat protein is a potent chemoattractant for basophils and lung mast cells, interacting with CCR3. Incubation of basophils with Tat protein upregulates the surface expression of the CCR3 receptor. There is evidence that human Fc epsilon RI(+) cells could be infected in vitro by M-tropic HIV-1 strains.
Basophils↗
The immunoglobulin superantigen-binding site of HIV-1 gp120 activates human basophils.
OBJECTIVE: To investigate the mechanism whereby HIV-1 envelope glycoprotein gp120 from four different isolates obtained in three different countries induces proinflammatory mediator release from normal human basophils. METHODS: Histamine, cysteinyl leukotriene C4 (LTC4) and interleukin 4 (IL-4) release into the supernatant was measured in gp120-stimulated peripheral blood basophils from HIV-1 and HIV-2 negative subjects. RESULTS: The HIV glycoprotein was a potent stimulus for release of these mediators in basophils purified from donors negative for HIV-1 and HIV-2. There was also a correlation (r = 0.58; P < 0.01) between the maximum IL-4 release from basophils induced by gp120 and by anti-IgE. Basophils from which IgE had been dissociated by brief exposure to lactic acid no longer released histamine in response to gp120 and anti-IgE. Anti-IgE specifically desensitized basophils to a subsequent challenge with anti-IgE and gp120. Human monoclonal IgM carrying the VH3 domain, but not that carrying the VH6 domain, inhibited gp120-induced secretion of histamine from basophils in a concentration-dependent manner. Synthetic peptides identical to regions distant from the N- and C-termini of gp120MN inhibited its activating capacity. CONCLUSIONS: gp120 acts as a viral superantigen interacting with the VH3 domain of IgE to induce the release of preformed and de novo synthesized mediators from human cells carrying the Fc fragment Fc epsilonRI receptor.
Adult↗
Secretory phospholipases A2 induce beta-glucuronidase release and IL-6 production from human lung macrophages.
Secretory phospholipases A2 (sPLA2s) are a group of extracellular enzymes that release fatty acids at the sn-2 position of phospholipids. Group IIA sPLA2 has been detected in inflammatory fluids, and its plasma level is increased in inflammatory diseases. To investigate a potential mechanism of sPLA2-induced inflammation we studied the effect of group IA (from cobra venom) and group IIA (human synovial) sPLA2s on human macrophages. Both sPLA2s induced a concentration- and Ca2+-dependent, noncytotoxic release of beta-glucuronidase (16.2 +/- 2.4% and 13.1 +/- 1.5% of the total content with groups IA and IIA, respectively). Both sPLA2s also increased the rate of secretion of IL-6 and enhanced the expression of IL-6 mRNA. Preincubation of macrophages with inhibitors of the hydrolytic activity of sPLA2 or cytosolic PLA2 did not influence the release of beta-glucuronidase. Incubation of macrophages with p-aminophenyl-mannopyranoside-BSA (mp-BSA), a ligand of the mannose receptor, also resulted in beta-glucuronidase release. However, while preincubation of macrophages with mp-BSA had no effect on beta-glucuronidase release induced by group IIA sPLA2, it enhanced that induced by group IA sPLA2. A blocking Ab anti-mannose receptor inhibited both mp-BSA- and group IIA-induced beta-glucuronidase release. Taken together, these data indicate that group IA and IIA sPLA2s activate macrophages with a mechanism independent from their enzymatic activities and probably related to the activation of the mannose receptor or sPLA2-specific receptors. The secretion of enzymes and cytokines induced by sPLA2s from human macrophages may play an important role in inflammation and tissue damage associated with the release of sPLA2s.
Aniline Compounds↗
Arachidonic acid metabolism in inflammatory cells of patients with bronchial asthma.
Over the last few years, the demonstration of beneficial effects of leukotriene receptor antagonists in various forms of asthma has renewed clinical and pharmacologic interest in this class of lipid mediators. Several studies demonstrated an increased biosynthesis of cysteinyl leukotrienes (CysLT) in asthmatic patients. However, the reasons for the dysregulated production of CysLTs in asthmatic patients are not completely defined. An improved method of lipid mediator detection and the availability of cells isolated from human airways (by bronchoalveolar lavage [BAL] and bronchial biopsies) have allowed initial studies to address this issue. Eosinophils retrieved from inflamed airways of asthmatics have a larger arachidonic acid (AA) content than their blood counterpart. The high level of AA in these cells is primarily due to a remodeling of endogenous arachidonate pools with the accumulation of this fatty acid in a triglyceride-associated pool. In addition, elevated levels of a secretory form of phospholipase A2, the key enzyme initiating the cascade of CysLTs, are found in the BAL of asthmatics. Finally, eosinophils isolated from the BAL of asthmatics have an increased expression of LTC4 synthase. The level of expression of this enzyme correlates with the increased amount of CysLTs produced in the airways of these patients. Taken together, these data identify at least two possible mechanisms to explain the excessive CysLT production in asthmatics: 1) an increased content of AA in the glycerolipid pools of inflammatory cells 2) an enhanced activity of key biosynthetic enzymes involved in CysLT synthesis.
Arachidonic Acid↗
Metabolism of lipid mediators in human eosinophils.
Explore the source record for details and available documents.
Arachidonic Acids↗
Mechanisms of IgE elevation in HIV-1 infection.
Serum IgE levels are high in adults and children with HIV-1 infection and could be a marker of poor prognosis. Allergic reactions and adverse reactions to drugs also tend to increase in HIV-1-infected individuals. An imbalance between a "T(H)1-like" and a "T(H)2-like" cytokine profile has been documented in HIV-1 infection. We have demonstrated that HIV-1 gp 120 from different clades is a stimulus for histamine and cytokine (IL-4 and IL-13) release from basophils. Gp 120 acts as a viral superantigen, interacting with the V(H)3 region of IgE to induce mediator release from human Fc epsilonRI+ cells. Human basophils and mast cells express the chemokine receptor CCR3, which binds the chemokines eotaxin and RANTES. By interacting with the CCR3 receptor on Fc epsilonRI+ cells, HIV-I Tat protein is a potent chemoattractant for human basophils and lung mast cells. Preincubation of basophils with Tat protein upregulates mRNA CCR3 and the surface expression of this chemokine receptor. Tat also induces IL-4 and IL-13 release from basophils. Extracellular Tat can influence the directional migration of human Fc epsilonRI+ cells, the expression of chemokine receptor CCR3, and the release of T(H)2 cytokines. Our results indicate two novel mechanisms by which two HIV-1 proteins, gp120 and Tat, trigger the release of cytokines critical for T(H)2 polarization from human Fc epsilonRI+ cells.
Gene Products, tat↗
Inhibition of platelet-activating factor synthesis in human neutrophils and platelets by propionyl-L-carnitine.
Propionyl-L-carnitine (PrC) has been shown to exert beneficial effects in the treatment of myocardial and peripheral ischemia in man. These conditions are associated with the activation of circulating neutrophils and platelets. To determine whether PrC could affect the synthesis of lipid mediators known to influence neutrophil and platelet functions, we explored the effects of PrC on the synthesis of platelet-activating factor (PAF) and arachidonic acid (AA) metabolites. Preincubation (90 min) of human neutrophils with PrC (0.1-100 microM) inhibited the synthesis of PAF and of a PAF analog (1-alkyl-1'enyl-2-acetyl-sn-glycero-3-phosphoethanolamine: AEGPE) induced in vitro by the calcium ionophore A23187. In contrast, concentrations of PrC up to 100 microM did not influence the uptake of exogenous AA or the A23187-induced release of AA and eicosanoids from neutrophils in vitro. PrC (1 microM) also inhibited PAF synthesis from human platelets stimulated in vitro with thrombin, but had no effect on thrombin-induced aggregation. Oral administration of PrC (2 g/day for two weeks) to five normal volunteers resulted in a significant inhibition of PAF and AEGPE synthesis by neutrophils stimulated with A23187 ex vivo, with no effect on AA or eicosanoid release. These data indicate that PrC selectively inhibits in vitro and ex vivo PAF synthesis from human neutrophils and platelets without influencing AA metabolism or eicosanoid release. This effect of PrC might represent an additional mechanism by which this molecule can exert protective effects in tissue ischemia and in other inflammatory diseases associated with neutrophil and platelet activation.
Adult↗