The double-edged sword of neutrophilic inflammation in bronchiectasis
Authors: Miguel Ángel Martínez-García, Concepción Prados Sánchez, Rosa María Girón Moreno
Journal: European Respiratory Journal (2015)

Bronchiectasis is a chronic inflammatory airway disease that is increasingly acquiring a greater epidemiological importance [1]. Its pathogenesis has two main characteristics: bronchial infection and bronchial inflammation. Although bronchial inflammation is mostly (but not always) caused by the bronchial infection, bronchial inflammation is an essential precondition for the development of bronchiectasis. On the cellular level, the inflammation predominantly comprises neutrophils [2]. The main molecules involved in the recruitment of neutrophils to the bronchial mucosa and the pulmonary parenchyma are interleukin (IL)-1β, tumour necrosis factor α, leukotriene β4 and especially some other cytokines from the CXC family, particularly CXCL8 (better known as IL-8) [2, 3]. These cytokines are distinguished by both low- and high-affinity receptors, designated as CXCR1 and CXCR2, respectively, and have been detected not only in neutrophils but also in a wide range of cells with pulmonary expression (endothelial cells, subsets of T-cells, macrophages, monocytes, eosinophils, basophils, epithelial cells, dendritic cells, mast cells, fibroblasts, type II pneumocytes and smooth muscle cells). CXCR1 and CXCR2 have been shown to be involved in the pathogenesis of various inflammatory and fibrotic pulmonary diseases [3, 4]. In humans CXR1 has been particularly associated with neutrophil degranulation and phagocytosis, while CXCR2 has been related to the adhesion and subsequent chemotaxis of these cells on the site of infection [3]. Increases in both the total number and the percentage of neutrophils, as well as the concentration of some neutrophilic proteolytic molecules (basically neutrophilic elastase (NE), myeloperoxidase (MPO) and metalloproteinase (MMP)-9) have been observed in several airway compartments. In addition they have been associated with greater structural changes as they are capable of damaging all the components of the bronchial wall, thereby destroying it and limiting its capacity to repair itself, resulting in the bronchial dilation characteristic of bronchiectasis [5]. All this means that the two key points for controlling the pathophysiological cascade of neutrophilic inflammation are the blockade of the proteolitic molecules produced by the neutrophils themselves, particularly NE (as reported in studies undertaken on bronchiectasis patients [6]), and, secondly, the blockade of CXCR1 and, more specifically, the selective blockade of CXCR2, which reduces bronchial neutrophilic inflammation by preventing the chemotaxis of these cells on the infection site [3]. However, we must remember that neutrophils are also one of the main lines of defence against bacterial infection and other microorganisms found in most bronchiectasis patients, and that bacterial products with a proteolitic capacity play a role in worsening the progression of the disease [2]. Inflammation in bronchiectasis: the therapeutic target of the future <http://ow.ly/Rlliw>