Roles of platelets in pathogenesis of aspirin-exacerbated respiratory disease


Published Online: July 17, 2015

Aspirin-exacerbated respiratory disease (AERD) is characterized by persistent eosinophilic inflammation in the airways, combined with hypersensitivity to cyclooxygenase-1 inhibitors and cysteinyl leukotriene (cysLT) overproductions. Additionally, hypersensitivity reaction and aspirin desensitization are possibly induced by low-dose aspirin, which inhibits mainly COX-1 but not COX-2. As platelets cannot express COX-2 because they lack nuclei, they produce prostanoids mainly via COX-1. Accordingly, it is possible that platelets play an important role in the pathogenesis of AERD. Laidlaw et al. reported that the number of platelet-adherent leukocytes increased in blood and nasal tissues in AERD patients might contribute to cysLT overproductions by transcellular metabolism of leukotrienes from leukocyte-derived LTA4 via LTC4S in platelets.

In a study recently published in The Journal of Allergy and Clinical Immunology (JACI), C. Mitsui and her colleagues of Sagamihara National Hospital assessed platelet activation under stable conditions and during an aspirin challenge test. The researchers analyzed the levels of two plasma markers (soluble P-selectin and soluble CD40 ligand), the expression levels of four surface markers on peripheral platelets [P-selectin, CD63, CD69, and GIIbIIIa (PAC-1)], and the frequencies of platelet-adherent leukocytes (eosinophils, neutrophils, basophils, and T lymphocytes) in patients under stable disease condition and control subjects. They also assessed the association of those markers with clinical parameters in AERD patients.

As a result, the levels of the two plasma markers, the expression levels of all four markers on platelets, and the frequency of platelet-adherent eosinophils were found to be higher in AERD patients than in aspirin-tolerant asthma (ATA) patients in a stable condition. There were no significant differences in the levels of these markers among ATA patients, idiopathic chronic eosinophilic pneumonia patients, and control subjects. The levels of some of the markers correlated with the frequency of platelet-adherent eosinophils associated with the concentration of uLTE4, and lung function. In contrast, the levels of platelet activation markers did not change during the aspirin challenge test in both the AERD patients and ATA patients.

The authors found that platelet activation, especially P-selectin, was related to cysLT overproduction and persistent airflow limitations in stable AERD patients. Suppression of platelet activation is a potential therapeutic target for severe eosinophilic inflammation in AERD.


The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI and is the most-cited journal in the field of allergy and clinical immunology.

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