Midkine is part of the antibacterial activity released at the surface of differentiated bronchial epithelial cells
(2013) In Journal of Innate Immunity 5(5). p.519-530- Abstract
To resist infections, robust defense mechanisms of the airways are essential. Retinoic acid promotes differentiation and maintains the phenotypic characteristics of bronchial epithelium. In addition, it induces the expression of the antibacterial growth factor midkine (MK). In the present study, we explored the expression and antibacterial activity of MK in an airway context. MK was detected in bronchial epithelial cells of large airways and type 2 pneumocytes of normal lungs by immunohistochemistry. Immunoelectron microscopy revealed a surface-associated distribution, both on the ciliated apical and basolateral sides, and MK was detected in sputum obtained from healthy individuals by ELISA. In vitro, MK killed the common respiratory... (More)
To resist infections, robust defense mechanisms of the airways are essential. Retinoic acid promotes differentiation and maintains the phenotypic characteristics of bronchial epithelium. In addition, it induces the expression of the antibacterial growth factor midkine (MK). In the present study, we explored the expression and antibacterial activity of MK in an airway context. MK was detected in bronchial epithelial cells of large airways and type 2 pneumocytes of normal lungs by immunohistochemistry. Immunoelectron microscopy revealed a surface-associated distribution, both on the ciliated apical and basolateral sides, and MK was detected in sputum obtained from healthy individuals by ELISA. In vitro, MK killed the common respiratory pathogen Streptococcus pneumoniae at below micromolar concentrations, an activity retained in the presence of sodium chloride at physiological concentrations. The MK molecule consists of two domains with three anti-parallel β-sheets and a COOH-terminal tail. Although both the NH2- and COOH-terminal domains alone showed antibacterial activity, the COOH-terminal domain including the tail region possessed higher bactericidal activity, i.e. in the order of the holoprotein. Retinoic acid-induced differentiation of primary bronchial epithelial cells, using an air-liquid interface system, revealed bactericidal activity in the apical airway surface liquid, an activity that was reduced after immunoprecipitation of MK. This study shows that airway epithelial cells of large airways and alveoli have a constitutive production of MK that is part of the bactericidal activity present in the air surface liquid, at least in vitro, and may thus be an important part of this arm of airway host defense.
(Less)
- author
- Nordin, Sara LU ; Andersson, Cecilia LU ; Bjermer, Leif LU ; Bjartell, Anders LU ; Mörgelin, Matthias LU and Egesten, Arne LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Bacteriolysis, Bronchi/immunology, Cell Differentiation, Cells, Cultured, Cytokines/chemistry, Gene Expression Regulation/immunology, Humans, Immunity, Innate, Midkine, Primary Cell Culture, Protein Conformation, Respiratory Mucosa/immunology, Sputum/metabolism, Streptococcus pneumoniae/physiology, Tretinoin/metabolism
- in
- Journal of Innate Immunity
- volume
- 5
- issue
- 5
- pages
- 12 pages
- publisher
- Karger
- external identifiers
-
- wos:000322098400010
- pmid:23391998
- scopus:84880920936
- pmid:23391998
- ISSN
- 1662-811X
- DOI
- 10.1159/000346709
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2013 S. Karger AG, Basel.
- id
- f64fefde-7bcc-4e44-a36a-a27d75104f12 (old id 3560032)
- date added to LUP
- 2016-04-01 10:28:46
- date last changed
- 2025-04-04 14:31:45
@article{f64fefde-7bcc-4e44-a36a-a27d75104f12,
abstract = {{<p>To resist infections, robust defense mechanisms of the airways are essential. Retinoic acid promotes differentiation and maintains the phenotypic characteristics of bronchial epithelium. In addition, it induces the expression of the antibacterial growth factor midkine (MK). In the present study, we explored the expression and antibacterial activity of MK in an airway context. MK was detected in bronchial epithelial cells of large airways and type 2 pneumocytes of normal lungs by immunohistochemistry. Immunoelectron microscopy revealed a surface-associated distribution, both on the ciliated apical and basolateral sides, and MK was detected in sputum obtained from healthy individuals by ELISA. In vitro, MK killed the common respiratory pathogen Streptococcus pneumoniae at below micromolar concentrations, an activity retained in the presence of sodium chloride at physiological concentrations. The MK molecule consists of two domains with three anti-parallel β-sheets and a COOH-terminal tail. Although both the NH2- and COOH-terminal domains alone showed antibacterial activity, the COOH-terminal domain including the tail region possessed higher bactericidal activity, i.e. in the order of the holoprotein. Retinoic acid-induced differentiation of primary bronchial epithelial cells, using an air-liquid interface system, revealed bactericidal activity in the apical airway surface liquid, an activity that was reduced after immunoprecipitation of MK. This study shows that airway epithelial cells of large airways and alveoli have a constitutive production of MK that is part of the bactericidal activity present in the air surface liquid, at least in vitro, and may thus be an important part of this arm of airway host defense. </p>}},
author = {{Nordin, Sara and Andersson, Cecilia and Bjermer, Leif and Bjartell, Anders and Mörgelin, Matthias and Egesten, Arne}},
issn = {{1662-811X}},
keywords = {{Bacteriolysis; Bronchi/immunology; Cell Differentiation; Cells, Cultured; Cytokines/chemistry; Gene Expression Regulation/immunology; Humans; Immunity, Innate; Midkine; Primary Cell Culture; Protein Conformation; Respiratory Mucosa/immunology; Sputum/metabolism; Streptococcus pneumoniae/physiology; Tretinoin/metabolism}},
language = {{eng}},
number = {{5}},
pages = {{519--530}},
publisher = {{Karger}},
series = {{Journal of Innate Immunity}},
title = {{Midkine is part of the antibacterial activity released at the surface of differentiated bronchial epithelial cells}},
url = {{http://dx.doi.org/10.1159/000346709}},
doi = {{10.1159/000346709}},
volume = {{5}},
year = {{2013}},
}