Mucins 3A and 3B Are Expressed in the Epithelium of Human Large Airway

Author:

Merikallio Heta12ORCID,Pincikova Terezia34,Kotortsi Ioanna35ORCID,Karimi Reza3,Li Chuan-Xing3,Forsslund Helena3,Mikko Mikael3,Nyrén Sven6,Lappi-Blanco Elisa7,Wheelock Åsa M.35,Kaarteenaho Riitta12,Sköld Magnus C.35

Affiliation:

1. Research Unit of Biomedicine and Internal Medicine, University of Oulu, 90570 Oulu, Finland

2. Center of Internal Medicine and Respiratory Medicine, Medical Research Center Oulu, University Hospital of Oulu, 90220 Oulu, Finland

3. Respiratory Medicine Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden

4. Stockholm CF-Center, Albatross, K56, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden

5. Department of Respiratory Medicine and Allergy, Karolinska University Hospital, 171 77 Stockholm, Sweden

6. Department of Molecular Medicine and Surgery, Division of Radiology, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden

7. Cancer and Translational Medicine Research Unit, Department of Pathology, University Hospital of Oulu, Oulu University, 90220 Oulu, Finland

Abstract

Aberrant mucus secretion is a hallmark of chronic obstructive pulmonary disease (COPD). Expression of the membrane-tethered mucins 3A and 3B (MUC3A, MUC3B) in human lung is largely unknown. In this observational cross-sectional study, we recruited subjects 45–65 years old from the general population of Stockholm, Sweden, during the years 2007–2011. Bronchial mucosal biopsies, bronchial brushings, and bronchoalveolar lavage fluid (BALF) were retrieved from COPD patients (n = 38), healthy never-smokers (n = 40), and smokers with normal lung function (n = 40). Protein expression of MUC3A and MUC3B in bronchial mucosal biopsies was assessed by immunohistochemical staining. In a subgroup of subjects (n = 28), MUC3A and MUC3B mRNAs were quantified in bronchial brushings using microarray. Non-parametric tests were used to perform correlation and group comparison analyses. A value of p < 0.05 was considered statistically significant. MUC3A and MUC3B immunohistochemical expression was localized to ciliated cells. MUC3B was also expressed in basal cells. MUC3A and MUC3B immunohistochemical expression was equal in all study groups but subjects with emphysema had higher MUC3A expression, compared to those without emphysema. Smokers had higher mRNA levels of MUC3A and MUC3B than non-smokers. MUC3A and MUC3B mRNA were higher in male subjects and correlated negatively with expiratory air flows. MUC3B mRNA correlated positively with total cell concentration and macrophage percentage, and negatively with CD4/CD8 T cell ratio in BALF. We concluded that MUC3A and MUC3B in large airways may be a marker of disease or may play a role in the pathophysiology of airway obstruction.

Funder

Jalmari and Rauha Ahokas Foundation

King Gustaf V’s and Queen Victoria’s Freemasons’ Foundation

Karolinska Institutet

Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and Karolinska Institutet

ERS-EU

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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