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Review
. 2020 Jul:157:104881.
doi: 10.1016/j.phrs.2020.104881. Epub 2020 May 4.

Granulocyte-targeted therapies for airway diseases

Luciana P Tavares  1 , Hong Yong Peh  2 , Wan Shun Daniel Tan  3 , Hadas Pahima  4 , Pasquale Maffia  5 , Ekaterini Tiligada  6 , Francesca Levi-Schaffer  7
Affiliations
Review

Granulocyte-targeted therapies for airway diseases

Luciana P Tavares et al. Pharmacol Res. 2020 Jul.

Abstract

The average respiration rate for an adult is 12-20 breaths per minute, which constantly exposes the lungs to allergens and harmful particles. As a result, respiratory diseases, which includes asthma, chronic obstructive pulmonary disease (COPD) and acute lower respiratory tract infections (LTRI), are a major cause of death worldwide. Although asthma, COPD and LTRI are distinctly different diseases with separate mechanisms of disease progression, they do share a common feature - airway inflammation with intense recruitment and activation of granulocytes and mast cells. Neutrophils, eosinophils, basophils, and mast cells are crucial players in host defense against pathogens and maintenance of lung homeostasis. Upon contact with harmful particles, part of the pulmonary defense mechanism is to recruit these cells into the airways. Despite their protective nature, overactivation or accumulation of granulocytes and mast cells in the lungs results in unwanted chronic airway inflammation and damage. As such, understanding the bright and the dark side of these leukocytes in lung physiology paves the way for the development of therapies targeting this important mechanism of disease. Here we discuss the role of granulocytes in respiratory diseases and summarize therapeutic strategies focused on granulocyte recruitment and activation in the lungs.

Keywords: Acute lower respiratory tract infections; Asthma; Chronic obstructive pulmonary disease; Granulocytes; Inflammation; Targeted therapy in the lungs.

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Conflict of interest statement

Declaration of Competing Interest The authors declared no conflict of interests.

Figures

Fig. 1
Fig. 1
Granulocytes in health and disease. Neutrophils, eosinophils, basophils and mast cells are crucial for the maintenance of lung health by preventing potential infections and inducing repair responses when needed. However, overactivation or recruitment of these cells can induce increased lung injury and bronchoconstriction, which aggravates and exacerbates respiratory diseases such as asthma, COPD, and lower respiratory tract infections. (Created with Biorender.com ®).
Fig. 2
Fig. 2
Granulocyte Mechanisms of Disease. Neutrophil activation and degranulation lead to the release of proteases, antimicrobial peptides, peroxidases, cytokines, and ROS that increase lung edema and damage lung epithelial and endothelial cells. Eosinophil, basophil and mast cells activation magnify type 2 responses while the secretion of proteases, histamine, leukotrienes and prostaglandins increase mucus secretion, bronchoconstriction and damage to the epithelial cells. (Created with Biorender.com ®).
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References

    1. Collaborators, G.B.D.L.R.I Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet Infect. Dis. 2018;18(11):1191–1210. - PMC - PubMed
    1. Collaborators, G.B.D.C.o.D Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the global burden of disease study 2016. Lancet. 2017;390(10100):1151–1210. - PMC - PubMed
    1. Brooks C.R. Sputum basophils are increased in eosinophilic asthma compared with non-eosinophilic asthma phenotypes. Allergy. 2017;72(10):1583–1586. - PubMed
    1. Rignault-Bricard R. IL-3-producing basophils are required to exacerbate airway hyperresponsiveness in a murine inflammatory model. Allergy. 2018;73(12):2342–2351. - PubMed
    1. Minai-Fleminger Y., Levi-Schaffer F. Mast cells and eosinophils: the two key effector cells in allergic inflammation. Inflamm. Res. 2009;58(10):631–638. - PubMed

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