Platelets, Not an Insignificant Player in Development of Allergic Asthma

Abstract

Allergic asthma is a chronic and heterogeneous pulmonary disease in which platelets can be activated in an IgE-mediated pathway and migrate to the airways via CCR3-dependent mechanism. Activated platelets secrete IL-33, Dkk-1, and 5-HT or overexpress CD40L on the cell surfaces to induce Type 2 immune response or interact with TSLP-stimulated myeloid DCs through the RANK-RANKL-dependent manner to tune the sensitization stage of allergic asthma. Additionally, platelets can mediate leukocyte infiltration into the lungs through P-selectin-mediated interaction with PSGL-1 and upregulate integrin expression in activated leukocytes. Platelets release myl9/12 protein to recruit CD4+CD69+ T cells to the inflammatory sites. Bronchoactive mediators, enzymes, and ROS released by platelets also contribute to the pathogenesis of allergic asthma. GM-CSF from platelets inhibits the eosinophil apoptosis, thus enhancing the chronic inflammatory response and tissue damage. Functional alterations in the mitochondria of platelets in allergic asthmatic lungs further confirm the role of platelets in the inflammation response. Given the extensive roles of platelets in allergic asthma, antiplatelet drugs have been tested in some allergic asthma patients. Therefore, elucidating the role of platelets in the pathogenesis of allergic asthma will provide us with new insights and lead to novel approaches in the treatment of this disease.

A method based on plateletpheresis to obtain functional platelet,CD3+andCD14+matched populations for research immunological studies

“…Platelets are anucleate blood cells generated from megakaryocytes. They are loaded with a wide range of mediators contained in secretory granules, which not only have coagulation‐related functions, but also play a key role in inflammation 1,2 . There is increasing evidence supporting the potential of platelets as a source of biomarkers in inflammatory diseases 3 .…”

“…They are loaded with a wide range of mediators contained in secretory granules, which not only have coagulation‐related functions, but also play a key role in inflammation. 1 , 2 There is increasing evidence supporting the potential of platelets as a source of biomarkers in inflammatory diseases. 3 This is particularly interesting in the field of allergy, in which severe allergy management often represents a difficult challenge.…”

Therapeutic effects of intranasal tocotrienol-rich fraction on rhinitis symptoms in platelet-activating factor induced allergic rhinitis

“…Allergic asthma is a chronic inflammatory disease leading to mucus hypersecretion, as well as the hyperresponsiveness, obstruction and remodelling in the airways. Upon allergen exposure, platelets entail in the IgE-FcεRI-dependent pathway, resulted in the infiltration of central effector cells in allergic inflammation, and the release of platelets-derived factors such as type 2 cytokines and various biochemical mediators including PAF [ 46 , 47 ]. ROS triggered by platelets also represent one of the contributing factors to allergic asthma.…”

Mechanisms Involved in the Stimulatory and Inhibitory Effects of 5-Hydroxytryptamine on Vagal Mechanosensitive Afferents in Rat Lung

“…5-HT also evoked an immediate stimulation of the silent RARs, which is mediated through direct activation of the 5-HT 3 receptors located on the sensory nerve terminals in these RARs. Given the fact that the increase of the 5-HT level in the lung is closely correlated with the severity of airway inflammatory diseases and the decline of pulmonary functions ( Cazzola and Matera, 2000 ; Luo et al, 2021 ), a possible involvement of these stimulatory effects of 5-HT on these mechanosensitive lung afferents in the manifestation of various symptoms and pathophysiological changes of lung functions should be recognized and considered.…”

“…5-hydroxytryptamine (5-HT) is a monoamine formed by decarboxylation of essential amino acid tryptophan, stored in secretory granules, and released from platelets and mast cells upon degranulation. Its diverse and complex pharmacological properties and physiological actions ( Adnot et al, 2013 ), and the significant role as an autacoid and chemical mediator in the pathogenesis of allergic airway inflammatory diseases such as asthma have been well recognized ( Cazzola and Matera, 2000 ; Luo et al, 2021 ). In addition, a profound bronchoconstrictive effect of 5-HT on both central and peripheral airways has been reported in various animal species ( Macquin-Mavier et al, 1991 ; Cazzola et al, 1995 ; Szarek et al, 1995 ).…”