Work

Intelectin-1 Is a Prominent Protein Constituent of Pathologic Mucus Associated with Eosinophilic Airway Inflammation in Asthma

Year: 2014

Type: article

Abstract: To the Editor:Intelectin-1 (ITLN-1) is an epithelial cell protein that is up-regulated in asthma (1).ITLN-1 is a pleotropic adipokine (also known as omentin-1) with roles in the gut ranging from host defense against pathogenic bacteria to promotion of insulin-stimulated glucose uptake (2-4).The host defense roles of ITLN-1 may result from its ability to bind structures expressed by microorganisms in a carbohydrate-dependent manner (5).ITLN-1 is also a binding partner for lactoferrin (6), and ITLN-1 may cooperate with lactoferrin in host defense (6, 7).Little is known about the function of ITLN-1 in human asthma.One possibility is that it participates in pathways of inflammation downstream of IL-13 (1).Indeed, studies in a mouse model of asthma suggest that ITLN-1 mediates IL-13-induced monocyte chemotactic protein-1 and -3 production in epithelial cells (8).Another possibility is that ITLN-1 is a component of airway mucus and contributes to pathologic mucus gel formation in disease.Supporting this possibility are studies in the gastrointestinal tract showing that ITLN-1 is a goblet cell protein that is secreted with mucus into the intestinal lumen (9).In addition, other studies in the intestine have suggested mucin-intelectin interactions that could alter the biophysical properties of mucus (10).Some of the results of these studies have been previously reported in the form of an abstract (11)Because mucus pathology causes mucus plugging and airway occlusion (12, 13), especially in fatal asthma ( 14), we set out to determine if ITLN-1 is a component of pathologic mucus in acute asthma.We first immunostained lung tissue sections from cases of fatal asthma and found prominent ITLN-1 immunostaining in the pathologic mucus plugs that occlude the airways (Figures 1A-1C).The cellular source of the ITLN-1 appears to be goblet cells (Figure 1C).We next measured ITLN-1 protein in sputum from 11 patients with acute severe asthma and two control groups (35 subjects with chronic stable asthma and 11 healthy control subjects) (Table 1).We found that ITLN-1 protein levels in the subgroup of patients with asthma in exacerbation were significantly higher than in stable asthma and in healthy control subjects (Figure 1D).We also noted that the increase in ITLN-1 in acute asthma was driven by the subgroup with increased sputum eosinophils (.2%) (Figure 1E), a finding that is consistent with ITLN-1's regulation by IL-13 in airway epithelial cells (1).ITLN-1 up-regulation is thus a feature of "Th2-high" asthma, and the known pathologic characteristics of this disease endotype can be extended to include high ITLN-1 protein concentrations in mucus forming during disease exacerbations.The prominent immunostaining for ITLN-1 in mucus plugs in fatal asthma and the high concentrations of ITLN-1 in sputum in acute severe asthma prompted us to explore if ITLN-1 can bind to human airway mucins.

Source: American Journal of Respiratory and Critical Care Medicine

DOI: 10.1164/rccm.201312-2220le