Platelet activation in allergic asthma patients during allergen challenge with <i>Dermatophagoides pteronyssinus</i>

Kowal, Krzysztof; Pampuch, Agnieszka; Kowal-Bielecka, Otylia; DuBuske, L.M.; Bodzenta-Łukaszyk, Anna

doi:10.1111/j.1365-2222.2006.02446.x

Cited by 100 publications

(120 citation statements)

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“…LPAs play important roles in secondary capture for leukocyte entry into inflamed tissues, including lung (26,27,38). Asthmatic responses are associated with platelet activation (39,40) and increased circulating LPAs have been detected in asthma attacks and after allergen challenge (39,41). These LPAs can also serve as important sources for bioactive lipid mediators, including LTs and LXs (25,33).…”

Section: Discussionmentioning

confidence: 99%

Lipoxin Generation Is Related to Soluble Epoxide Hydrolase Activity in Severe Asthma

Ono

Dutile

Kazani

et al. 2014

Am J Respir Crit Care Med

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Rationale: Severe asthma is characterized by airway inflammatory responses associated with aberrant metabolism of arachidonic acid. Lipoxins (LX) are arachidonate-derived pro-resolving mediators that are decreased in severe asthma, yet mechanisms for defective LX biosynthesis and a means to increase LXs in severe asthma remain to be established.Objectives: To determine if oxidative stress and soluble epoxide hydrolase (sEH) activity are linked to decreased LX biosynthesis in severe asthma.Methods: Aliquots of blood, sputum, and bronchoalveolar lavage fluid were obtained from asthma subjects for mediator determination. Select samples were exposed to t-butyl-hydroperoxide or sEH inhibitor (sEHI) before activation. Peripheral blood leukocyte-platelet aggregates were monitored by flow cytometry, and bronchial contraction was determined with cytokine-treated human lung sections.Measurements and Main Results: 8-Isoprostane levels in sputum supernatants were inversely related to LXA 4 in severe asthma (r = 20.55; P = 0.03) and t-butyl-hydroperoxide decreased LXA 4 and 15-epi-LXA 4 biosynthesis by peripheral blood leukocytes. LXA 4 and 15-epi-LXA 4 levels were inversely related to sEH activity in sputum supernatants and sEHIs significantly increased 14,15-epoxy-eicosatrienoic acid and 15-epi-LXA 4 generation by severe asthma whole blood and bronchoalveolar lavage fluid cells. The abundance of peripheral blood leukocyte-platelet aggregates was related to asthma severity. In a concentration-dependent manner, LXs significantly inhibited plateletactivating factor-induced increases in leukocyte-platelet aggregates (70.8% inhibition [LXA 4 100 nM], 78.3% inhibition [15-epi-LXA 4 100 nM]) and 15-epi-LXA 4 markedly inhibited tumor necrosis factora-induced increases in bronchial contraction.Conclusions: LX levels were decreased by oxidative stress and sEH activity. Inhibitors of sEH increased LXs that mediated antiphlogistic actions, suggesting a new therapeutic approach for severe asthma. Clinical trial registered with www.clinicaltrials.gov (NCT 00595114).

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Section: Discussionmentioning

confidence: 99%

Lipoxin Generation Is Related to Soluble Epoxide Hydrolase Activity in Severe Asthma

Ono

Dutile

Kazani

et al. 2014

Am J Respir Crit Care Med

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“…55,56 In addition, increased circulating plateletleukocyte aggregates have been detected in patients with asthma attacks and after allergen challenge. 57,58 Similarly, allergenchallenged mice showed platelet-leukocyte complexes in their circulation. 59 Importantly, platelets expressing P-selectin on their surface are required for the influx of eosinophils into the lungs of mice with allergic inflammation, as indicated by experiments with platelet-depleted mice transfused with either wild-type platelets (which restored eosinophil recruitment) or P-selectin-deficient platelets (which failed to do so).…”

Section: Platelets and Asthmamentioning

confidence: 99%

Asthma and coagulation

Boer

Majoor²,

Veer

et al. 2012

Blood

145

140

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Asthma is a chronic airway disease characterized by paroxysmal airflow obstruction evoked by irritative stimuli on a background of allergic lung inflammation. Currently, there is no cure for asthma, only symptomatic treatment. In recent years, our understanding of the involvement of coagulation and anticoagulant pathways, the fibrinolytic system, and platelets in the pathophysiology of asthma has increased considerably. Asthma is associated with a procoagulant state in the bronchoalveolar space, further aggravated by impaired local activities of the anticoagulant protein C system and fibrinolysis. Protease-activated receptors have been implicated as the molecular link between coagulation and allergic inflammation in asthma. This review summarizes current knowledge of the impact of the disturbed hemostatic balance in the lungs on asthma severity and manifestations and identifies new possible targets for asthma treatment. (Blood. 2012;119(14):3236-3244) IntroductionAsthma is a disease of chronic airway inflammation causing symptoms of paroxysmal airflow obstruction, airway hyperresponsiveness to irritative stimuli, wheezing, chest tightness, and coughing. 1 These symptoms occur against a background of allergic inflammation, characterized by infiltration of mast cells, eosinophils, and T-helper 2 (Th2) lymphocytes into the airway wall and mucus hypersecretion. Many patients with chronic asthma show progressive decline of lung function that is thought to be the result of structural remodeling of the airway wall 2 and have frequent exacerbations and steroid resistance, 3 posing a major clinical challenge and health problem. 4 New therapeutic approaches need to be developed targeting the inflammatory background that triggers asthma symptoms. 5 Historically, coagulation and fibrinolysis have been considered as processes that take place in the vascular compartment. It is now appreciated that the airways represent a body compartment in which coagulation and anticoagulant mechanisms can be initiated and regulated locally. 6 In addition to the activation of coagulation in lung inflammatory disorders that is probably induced by leakage of plasma proteins into the bronchoalveolar space, essential mediators of coagulation can be found locally in the lung, including tissue factor (TF) that initiates coagulation and thrombin, which transforms fibrinogen to fibrin. 7 Several diseases associated with abundant lung inflammation, including acute respiratory distress syndrome, pneumonia, and lung fibrosis, 6,8 have been shown to result in similar changes in bronchoalveolar levels of proteins implicated in coagulation and fibrinolysis, tipping the physiologic equilibrium of preventing fibrin clot formation toward a net procoagulant state. In particular, for asthma this disturbed hemostatic balance in the airways is of importance for the perpetuation of allergic inflammation (Figure 1) in which cytokines and protease-activated receptors (PARs) play an important role. In addition, platelets have been found to actively participate in ma...

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“…In addition, platelets are localized to various tissue compartments in the lung parenchyma of biopsies taken from asthmatic patients (Metzger et al, 1987;Jeffery et al, 1989) and this event is accompanied with bone marrow karyopoiesis and thrombopoiesis (Slater et al, 1985). This is perhaps the result of localized platelet recruitment and activation within lungs, since circulating venous platelet numbers have been shown to fall during both early-and late-phase responses to allergen (Kowal et al, 2006). Platelet-platelet, and platelet-leukocyte aggregates have also been detected in patients with spontaneous asthma attacks (Gresele et al, 1993).…”

Section: Platelet Activation In Asthma and Rhinitismentioning

confidence: 99%

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Pitchford

2007

British J Pharmacology

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An alteration in the character and function of platelets is manifested in patients with inflammatory diseases, and these alterations have been dissociated from the well‐characterized involvement of platelets in thrombosis and haemostasis. Recent evidence reveals platelet activation is sometimes critical in the development of inflammation. The mechanisms by which platelets participate in inflammation are diverse, and offer numerous opportunities for future drug intervention. There is now acceptance that platelets act as innate inflammatory cells in immune responses, with roles as sentinel cells undergoing surveillance, responding to microbial invasion, orchestrating leukocyte recruitment, and migrating through tissue, causing damage and influencing repair processes in chronic disease. Some of these processes are targeted by drugs that are being developed to target platelet participation in atherosclerosis. The actions of platelets therefore influence the pathogenesis of diverse inflammatory diseases in various body compartments, encompassing parasitic and bacterial infection, allergic inflammation (especially asthma and rhinitis), and non‐atopic inflammatory conditions, for example, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and atherosclerosis. This review will first discuss the evidence for platelet activation in these various inflammatory diseases, and secondly discuss the mechanisms by which this pathogenesis occurs and the various anti‐platelet agents which have been developed to combat platelet activation in atherosclerosis and their potential future use for the treatment of other inflammatory diseases.British Journal of Pharmacology (2007) 152, 987–1002; doi:10.1038/sj.bjp.0707364; published online 2 July 2007

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Platelet activation in allergic asthma patients during allergen challenge with Dermatophagoides pteronyssinus

Abstract: In allergic asthma patients development of prolonged airway inflammation after allergen challenge is associated with intravascular platelet activation.

Cited by 100 publications

References 29 publications

Lipoxin Generation Is Related to Soluble Epoxide Hydrolase Activity in Severe Asthma

Lipoxin Generation Is Related to Soluble Epoxide Hydrolase Activity in Severe Asthma

Asthma and coagulation

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

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