<p>The Role of Mast Cells in Aspirin-Exacerbated Respiratory Disease (AERD) Pathogenesis: Implications for Future Therapeutics</p>

Abstract

Mast cells (MC) have recently been demonstrated to play an integral role in the pathogenesis of aspirin-exacerbated respiratory disease (AERD). When activated, MCs release pre-formed granules of many pro-inflammatory mediators, including histamine, serotonin, and various chemokines and cytokines including tumor necrosis factor (TNF)-α, interferon ɣ (IFN ɣ), macrophage inhibitory factor, transforming growth factor, interleukin (IL) 1, 3-6, 9, 10, 13 and 16. These mediators promote inflammation in AERD by recruiting or activating a network of cells involved in acute and chronic inflammatory pathways, such as endothelial, epithelial, stromal, and other immune cells. Several studies have implicated multifactorial pathways for MC activation in AERD beyond classical IgE mediated mechanisms. The elucidation of these complex networks therefore represents important targets for innovative patient therapeutics. This review summarizes classic and alternative pathways of MC activation in AERD with a special focus in relation to new and emerging treatment strategies.

Emerging Biomarkers Beyond Leukotrienes for the Management of Nonsteroidal Anti-inflammatory Drug (NSAID)-Exacerbated Respiratory Disease

“… 50 Mast cell activation is mediated by both IgE-dependent and -independent mechanisms. 48 The IgE level was significantly higher in the NP tissue from NERD patients than from ATA patients with CRS with/without NP, and was associated with faster recurrence of NP. 51 In addition, IgE antibodies to staphylococcal enterotoxins enhanced eosinophil activation of NPs in patients with NERD.…”

“…2 ). 40 43 47 48 The number of mast cells was reported to be higher in bronchial biopsies of NERD patients than of ATA patients ( Table ), 49 and elevated levels of serum tryptase during aspirin challenges in NERD patients reflected mast cell activation. 50 Mast cell activation is mediated by both IgE-dependent and -independent mechanisms.…”

Perfil clínico epidemiológico de pacientes com doença respiratória exacerbada por aspirina (DREA) em centro de referência

“…Também há os pacientes que apresentam fenótipo com reação cutânea ou até anafilaxia (LEE et al, 2017). A doença progride mesmo na ausência da exposição aos AINEs (LAIDLAW; LEVY, 2020;WOESSNER, 2017).…”

“…Há diminuição na produção de prostaglandina E2 (PGE2), que tem atividade antiinflamatória, com diminuição dos receptores de prostaglandina E2(EP2), os quais são críticos para inibir a ativação de mastócitos e eosinófilos (KURUVILLA; VANIJCHAROENKARN;LEVY, 2020;PEREZ-NOVO et al, 2005;SCHMID et al, 1999).…”

“…IL-4 e IFN-gama aumentam a expressão de LTC4 sintetase em mastócitos e eosinófilos. (KURUVILLA; VANIJCHAROENKARN;LEVY, 2020;STEINKE et al, 2013c).…”