Airway Platelet Activation is Associated with Airway Eosinophilic Inflammation in Asthma

Benton, Angela S.; Kumar, Nikila; Lerner, Jennifer S.; Wiles, Andrew A.; Foerster, Matthew; Teach, Stephen J.; Freishtat, Robert J.

doi:10.2310/jim.0b013e3181fa02f7

Cited by 30 publications

(28 citation statements)

References 26 publications

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“…For every log 10 unit increase in CypA there was a 2.973 unit decrease in log 10 FEV 1 change with bronchodilator (−2.973 [−4.887, −1.059]; adjusted P =0.003), indicating a worse response to the bronchodilator drug. Based on recently published observations that platelet activation correlates with airway eosinophilia in asthma (25), we also examined whether levels of CypA or CypB might be associated with platelet activation in asthmatic airways. Both Cyps were associated with levels of P-selectin, which is a measurement of platelet activation (CypA: 0.418 [0.153, 0.683], adjusted P =0.002; CypB: 0.842 [0.018, 1.665]; adjusted P =0.045).…”

Section: Resultsmentioning

confidence: 99%

“…Studies have demonstrated not only that CypA can be released from activated platelets (46), but also that CypB increases platelet adhesion to collagen (47). Further, platelet activation has also been shown to be important for leukocyte activation and recruitment into tissues (25, 48). Thus, Cyps have the potential to be involved in many aspects of asthma pathology, from leukocyte activation and recruitment, to airway remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…The AsthMaP Project is described in detail elsewhere (25-28). Briefly, 154 participants aged 6-20 years, with physician-diagnosed asthma for at least one year (with varying chronic asthma therapy), were recruited from the Children’s National Emergency Department.…”

Section: Methodsmentioning

confidence: 99%

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Extracellular Cyclophilin Levels Associate with Parameters of Asthma in Phenotypic Clusters

et al. 2011

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Objective Leukocyte persistence during chronic (quiescent) phases of asthma is a major hallmark of the disease. The mechanisms regulating these persistent leukocyte populations are not clearly understood. An alternative family of chemoattracting proteins, cyclophilins, has recently been shown to contribute to leukocyte recruitment in animal models of allergic asthma. The goal of this study was to determine if cyclophilins are present in asthma patients during the chronic phase of disease, and to investigate whether levels of cyclophilins associate with clinical parameters of disease severity. Methods Nasal wash samples from an urban cohort of 137 6- to 20-year olds with physician-diagnosed asthma were examined for the presence of cyclophilin A (CypA), cyclophilin B (CypB), as well as several other classical chemokines. Linear, logistic, or ordinal regressions were performed to identify associations between cyclophilins, chemokines, and clinical parameters of asthma. The asthma cohort was further divided into previously established phenotypic clusters (Cluster 1 n=55; cluster 2 n=31; and cluster 3 n=51), and examined for associations. Results Levels of CypB in the asthma group were highly elevated compared to non-asthmatic controls, while a slight increase in MCP-1 was also observed. CypA and MCP-1 were associated with levels of eosinophil cationic protein (ECP; a marker of eosinophil activation). Cluster-specific associations were found for CypA and CypB and clinical asthma parameters [e.g. forced expiratory volume in 1 second (FEV1) and ECP]. Conclusions Cyclophilins are present in nasal wash samples of asthma patients and may be a novel biomarker for clinical parameters of asthma severity.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Extracellular Cyclophilin Levels Associate with Parameters of Asthma in Phenotypic Clusters

et al. 2011

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“…Recently, we demonstrated that TSLP could be induced to express in vascular endothelial and smooth muscle cells by angiotensin II and oxidized-low-density lipoprotein [26] and over-expressed in human atherosclerotic artery specimens [27], which indicated that TSLP/TSLPR might play roles in atherosclerosis. Therefore, TSLP is not only associated with inflammatory and allergy diseases but also plays important roles in atherosclerosis, which has been linked to platelet activation and the probability of thrombosis [28,29,30,31]. …”

Section: Introductionmentioning

confidence: 99%

Inflammatory Cytokine TSLP Stimulates Platelet Secretion and Potentiates Platelet Aggregation via a TSLPR-Dependent PI3K/Akt Signaling Pathway

Dong

Lin

Wang

et al. 2015

Cell Physiol Biochem

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Aims: Thymic stromal lymphopoietin (TSLP) plays an important role in inflammatory diseases and is over-expressed in human atherosclerotic artery specimens. The present study investigated the role of TSLP in platelet activation and thrombosis models in vitro and in vivo, as well as the underlying mechanism and signaling pathway. Methods and Results: Western blotting and flow cytometry demonstrated that the TSLP receptor was expressed on murine platelets. According to flow cytometry, platelet stimulation with TSLP induced platelet degranulation and integrin αIIbβ3 activation. A TSLPR deficiency caused defective platelet aggregation, defective platelet secretion and markedly blunted thrombus growth in perfusion chambers at both low and high shear rates. TSLPR KO mice exhibited defective carotid artery thrombus formation after exposure to FeCl₃. TSLP increased Akt phosphorylation, an effect that was abrogated by the PI3K inhibitors wortmannin and LY294002. The PI3K inhibitors further diminished TSLP-induced platelet activation. TSLP-mediated platelet degranulation, integrin αIIbβ3 activation and Akt phosphorylation were blunted in platelets that lacked the TSLP receptor. Conclusion: This study demonstrated that the functional TSLPR was surface-expressed on murine platelets. The inflammatory cytokine TSLP triggered platelet activation and thrombus formation via TSLP-dependent PI3K/Akt signaling, which suggests an important role for TSLP in linking vascular inflammation and thrombo-occlusive diseases.

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“…20 Identifying the role of platelets in the development of allergic asthma will not only benefit our understanding of the molecular and cellular mechanisms of allergic asthma but may also provide potential targets for therapy of this disease. Although previous studies showed evidence of platelet activation, [21][22][23] as well as of the involvement of CD154 24 in asthma, the exact role of platelet activation and the underlying mechanisms in the progression of allergic asthma remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Platelets promote allergic asthma through the expression of CD154

et al. 2014

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Platelet activation is associated with multiple immune responses and the pathogenesis of various immune-related diseases. However, the exact role and the underlying mechanism of platelets in the progression of allergic asthma remain largely unclear. In this study, we demonstrate that during antigen sensitization, platelets can be activated by ovalbumin (OVA) aerosol via the upregulation of CD154 (CD40L) expression. Platelet transfer promoted allergic asthma progression by inducing more severe leukocyte infiltration and lung inflammation, elevated IgE production and strengthened T helper 2 (Th2) responses in asthma-induced mice. Accordingly, platelet depletion compromised allergic asthma progression. Cd154-deficient platelets failed to promote asthma development, indicating the requirement of CD154 for platelets to promote asthma progression. The mechanistic study showed that platelets inhibited the induction of Foxp3 1 regulatory T cells both in vivo and in vitro at least partially through CD154, providing an explanation for the increase of Th2 responses by platelet transfer. Our study reveals the previously unknown role of platelet CD154 in the promotion of asthma progression by polarizing Th2 responses and inhibiting regulatory T-cell generation and thus provides a potential clue for allergic disease interventions.

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Airway Platelet Activation is Associated with Airway Eosinophilic Inflammation in Asthma

Cited by 30 publications

References 26 publications

Extracellular Cyclophilin Levels Associate with Parameters of Asthma in Phenotypic Clusters

Extracellular Cyclophilin Levels Associate with Parameters of Asthma in Phenotypic Clusters

Inflammatory Cytokine TSLP Stimulates Platelet Secretion and Potentiates Platelet Aggregation via a TSLPR-Dependent PI3K/Akt Signaling Pathway

Platelets promote allergic asthma through the expression of CD154

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