Possible Mechanisms of Eosinophil Accumulation in Eosinophilic Pneumonia

Abstract

Eosinophilic pneumonia (EP), including acute EP and chronic EP, is characterized by the massive pulmonary infiltration of eosinophils into the lung. However, the mechanisms underlying the selective accumulation of eosinophils in EP have not yet been fully elucidated. We reported that bronchoalveolar lavage fluid (BALF) from EP patients induced the transmigration of eosinophils across endothelial cells in vitro. The concentrations of eotaxin-2 (CCL24) and monocyte chemotactic protein (MCP)-4 (CCL13), which are CC chemokine receptor (CCR) 3 ligands, were elevated in the BALF of EP patients, and anti-CCR3 monoclonal antibody inhibited the eosinophil transmigration induced by the BALF of EP patients. The concentration of macrophage inflammatory protein 1β (CCL4), a CCR5 ligand that induces eosinophil migration, was increased in the BALF of EP patients. Furthermore, the concentration of interleukin (IL) 5 was increased in the BALF of EP patients, and it has been reported that anti-IL-5 antibody treatment resulted in remission and the reduction of glucocorticoid use in some cases of chronic EP. The concentrations of lipid mediators, such as leukotriene (LT) B 4 , damage-associated molecular pattern molecules (DAMPs), such as uric acid, or extracellular matrix proteins, such as periostin, were also increased in the BALF of EP patients. These findings suggest that chemokines, such as CCR3/CCR5 ligands, cytokines, such as IL-5, lipid mediators, such as LTB 4 , DAMPs, and extracellular matrix proteins may play roles in the accumulation or activation of eosinophils in EP.Biomolecules 2020, 10, 638 2 of 12 mechanisms of eosinophil accumulation in the airway of EP patients are discussed. The aim of this review is to better understand the mechanisms of eosinophil accumulation and activation in EP. AEP and CEPAEP is characterized by acute febrile illness with diffuse pulmonary infiltrates, severe hypoxemia, and increased eosinophils in bronchoalveolar lavage fluid (BALF) [3]. AEP is diagnosed based on the following: acute onset of respiratory failure, diffuse pulmonary infiltrates on chest roentgenogram, and increased numbers of eosinophils in BALF (more than 25% of total cells) [3]. Although the mechanisms of AEP have not yet been fully established, inhaled agents, such as cigarette smoke or chemical agents, are known causes of AEP [1,2,[5][6][7][8][9]. For example, a relationship was observed between the recent onset of cigarette smoking and the development of AEP [5][6][7]. Even short-term passive smoking can induce AEP [7]. The collapse of the World Trade Center towers [8] and the desert of the Middle East [9] have also been reported to induce AEP.

Vinpocetine alleviates lung inflammation via macrophage inflammatory protein-1β inhibition in an ovalbumin-induced allergic asthma model

“…MIP-1β is a well-known chemokine produced by various cells, such as neutrophils, epithelial cells, B cells, T cells, and eosinophils [ 55 ]. In a previous study, MIP-1β was found to have chemo-attractant activity for eosinophils [ 56 ]. These chemo-attractant activities of MIP-1β can cause the infiltration of eosinophils into the lungs and bronchi, which results in allergic lung inflammation [ 8 ].…”

Emerging Evidence for Pleiotropism of Eosinophils

“…IL-5 acts synergistically with eotaxins, a variety of C-C motif chemokine ligands (CCLs), which are selective chemotactic factors that mediate the migration and recruitment of these cells into the body tissues and their activation [30]. Eotaxin (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26), among others, bind to CCchemokine receptors-3 (CCR3) on eosinophil cell membranes and can induce chemotaxis in allergic inflammation [31] (Figure 1). 5-oxo 6, 8, 11, 14-eicosatetraenoic acid (5-oxo-ETE) is another eosinophil chemoattractant [32].…”

Role of Allergen Immunotherapy in Asthma Treatment and Asthma Development

“…For circulating eosinophils to accumulate in asthmatic airways, they must adhere to and then migrate across vascular endothelial cells. These processes are largely regulated by cytokines/chemokines produced by various cells, including Th2 cells [44][45][46]. Increased adhesion of peripheral blood eosinophils and increased chemotactic activity of eosinophils into the airways are observed during the allergen exposure period in birch pollen asthma, and allergen immunotherapy suppresses increased eosinophil adhesion and chemotactic activity [3,32].…”