Alveolar epithelial cells direct monocyte transepithelial migration upon influenza virus infection: Impact of chemokines and adhesion molecules

Herold, Susanne and von Wulffen, Werner and Steinmueller, Mirko and Pleschka, Stephan and Kuziel, William A. and Mack, Matthias and Srivastava, Mrigank and Seeger, Werner and Maus, Ulrich A. and Lohmeyer, Juergen (2006) Alveolar epithelial cells direct monocyte transepithelial migration upon influenza virus infection: Impact of chemokines and adhesion molecules. JOURNAL OF IMMUNOLOGY, 177 (3). pp. 1817-1824. ISSN 0022-1767,

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Abstract

Influenza A virus pneumonia is characterized by severe lung injury and high mortality. Early infection elicits a strong recruitment of monocytes from the peripheral blood across the endo-/epithelial barrier into the alveolar air space. However, it is currently unclear which of the infected resident lung cell populations, alveolar epithelial cells or alveolar macrophages, elicit monocyte recruitment during influenza A virus infection. In the current study, we investigated whether influenza A virus infection of primary alveolar epithelial cells and resident alveolar macrophages would elicit a basal-to-apical monocyte transepithelial migration in vitro. We found that infection of alveolar epithelial cells with the mouse-adapted influenza A virus strain PR/8 strongly induced the release of monocyte chemoattractants CCL2 and CCL5 followed by a strong monocyte transepithelial migration, and this monocytic response was strictly dependent on monocyte CCR2 but not CCR5 chemokine receptor expression. Analysis of the adhesion molecule pathways demonstrated a role of ICAM-1, VCAM-I, integrin-associated protein (CD47), and junctional adhesion molecule-c on the epithelial cell surface interacting with monocyte 0, and 132 integrins and integrin-associated protein in the monocyte transmigration process. Importantly, addition of influenza A virus-infected alveolar macrophages further enhanced monocyte transmigration across virus-infected epithelium in a TNF-alpha-dependent manner. Collectively, the data show an active role for virus-infected alveolar epithelium in the regulation of CCL2/CCR2-dependent monocyte transepithelial migration during influenza infection that is essentially dependent on both classical beta(1) and beta(2) integrins but also junctional adhesion molecule pathways.

Item Type: Article
Uncontrolled Keywords: AERUGINOSA-INDUCED PNEUMONIA; A VIRUS; POLYMORPHONUCLEAR LEUKOCYTES; NEUTROPHIL TRANSMIGRATION; SURFACE EXPRESSION; GENE-EXPRESSION; PRIMARY CULTURE; INTACT MICE; PULMONARY; MACROPHAGES;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin II
Depositing User: Dr. Gernot Deinzer
Date Deposited: 09 Feb 2021 07:35
Last Modified: 09 Feb 2021 07:35
URI: https://pred.uni-regensburg.de/id/eprint/34239

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