Mucins MUC5B and MUC5AC in distal airways and honeycomb spaces: comparison among idiopathic pulmonary fibrosis/usual interstitial pneumonia, fibrotic …
C Conti, A Montero-Fernandez, E Borg… - American journal of …, 2016 - atsjournals.org
C Conti, A Montero-Fernandez, E Borg, T Osadolor, P Viola, A De Lauretis, CJ Stock…
American journal of respiratory and critical care medicine, 2016•atsjournals.orgAlthough the pathogenesis of idiopathic pulmonary fibrosis (IPF) remains elusive (1), one of
the most intriguing aspects concerns the possible role of mucins. A strong association has
been reported between the promoter polymorphism rs35705950 of MUC5B and the
occurrence of familial/sporadic IPF (2-10), as well as with a more benign disease course (10,
11). Overexpression of MUC5B and of the other main airway mucin, MUC5AC, has been
described in IPF lungs (12, 13), but the level of expression in other types of pulmonary …
the most intriguing aspects concerns the possible role of mucins. A strong association has
been reported between the promoter polymorphism rs35705950 of MUC5B and the
occurrence of familial/sporadic IPF (2-10), as well as with a more benign disease course (10,
11). Overexpression of MUC5B and of the other main airway mucin, MUC5AC, has been
described in IPF lungs (12, 13), but the level of expression in other types of pulmonary …
Although the pathogenesis of idiopathic pulmonary fibrosis (IPF) remains elusive (1), one of the most intriguing aspects concerns the possible role of mucins. A strong association has been reported between the promoter polymorphism rs35705950 of MUC5B and the occurrence of familial/sporadic IPF (2-10), as well as with a more benign disease course (10, 11). Overexpression of MUC5B and of the other main airway mucin, MUC5AC, has been described in IPF lungs (12, 13), but the level of expression in other types of pulmonary fibrosis is unknown. In this study, we compare MUC5B and MUC5AC expression among IPF, idiopathic nonspecific interstitial pneumonitis (i-NSIP), systemic sclerosis-associated NSIP (SSc-NSIP), and control lungs. Some of the results of this study have been previously reported in the form of an abstract (14).
Surgical lung biopsies from 23 patients with IPF/usual interstitial pneumonia (UIP)(17 men; mean 6 SD age, 59 6 10 yr; 16 ever-smokers), 18 with i-NSIP (10 men; mean, age 46 6 23 yr; 11 ever-smokers), and 15 with SSc-NSIP (4 men; mean age, 52 6 11 yr; 11 ever-smokers) and normal lung tissue peripheral to resected cancer from 10 smoker and 10 nonsmoker control subjects (11 men; mean age, 68 6 14 yr) were selected from the Royal Brompton Hospital pathology archive with ethical approval. No significant differences in FVC, diffusing capacity of the lung for carbon monoxide (DLCO), or composite physiologic index (15) were observed between the different fibrotic patterns with the exception of patients with SSc-NSIP, characterized by a significantly higher DLCO (FVC, 79 6 22, 79 6 15, and 78 6 26% of the predicted value, respectively, in IPF, SSc-NSIP, and i-NSIP; DLCO, 51 6 9, 58 6 8, and 48 6 15% of the predicted value; composite physiologic index, 41 6 10, 38 6 7, 47 6 14). Sequential sections were immunolabeled with MUC5B-and MUC5AC-specific antibodies (MUC5AC, Clone 45M1; Biocare Ltd., Concord, CA; and MUC5B, clone sc-20119, Santa Cruz Biotechnology, Dallas, TX; 1: 100 dilution for both). Distal airways were defined as airways with no cartilage support or glandular elements, surrounded by smooth muscle bands and characterized by an undulating epithelium. Honeycomb cysts were defined as mucus-
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