Coronin 1A, a novel player in integrin biology, controls neutrophil trafficking in innate immunity

Trafficking of polymorphonuclear neutrophils (PMNs) during inflammation critically depends on the β2 integrins lymphocyte function–associated antigen 1 (LFA-1) (CD11a/CD18) and macrophage-1 antigen (CD11b/CD18). Here, we identify coronin 1A (Coro1A) as a novel regulator of β2 integrins that interact...

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Bibliographic Details
Published in:Blood 2017-08, Vol.130 (7), p.847-858
Main Authors: Pick, Robert, Begandt, Daniela, Stocker, Thomas J., Salvermoser, Melanie, Thome, Sarah, Böttcher, Ralph T., Montanez, Eloi, Harrison, Ute, Forné, Ignasi, Khandoga, Alexander G., Coletti, Raffaele, Weckbach, Ludwig T., Brechtefeld, Doris, Haas, Rainer, Imhof, Axel, Massberg, Steffen, Sperandio, Markus, Walzog, Barbara
Format: Article
Language:English
Subjects:
4-Butyrolactone - analogs & derivatives
4-Butyrolactone - metabolism
Actins - metabolism
Animals
Calcium Signaling
CD18 Antigens - metabolism
Cell Adhesion
Cell Movement
Gastritis - immunology
Gastritis - microbiology
Gastritis - pathology
Helicobacter pylori - physiology
Immunity, Innate
Lymphocyte Function-Associated Antigen-1 - metabolism
Macrophage-1 Antigen - metabolism
Mice, Inbred C57BL
Neutrophils - cytology
Neutrophils - metabolism
Receptors, G-Protein-Coupled - metabolism
Rheology
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Summary:Trafficking of polymorphonuclear neutrophils (PMNs) during inflammation critically depends on the β2 integrins lymphocyte function–associated antigen 1 (LFA-1) (CD11a/CD18) and macrophage-1 antigen (CD11b/CD18). Here, we identify coronin 1A (Coro1A) as a novel regulator of β2 integrins that interacts with the cytoplasmic tail of CD18 and is crucial for induction of PMN adhesion and postadhesion events, including adhesion strengthening, spreading, and migration under flow conditions. Transition of PMN rolling to firm adhesion critically depends on Coro1A by regulating the accumulation of high-affinity LFA-1 in focal zones of adherent cells. Defective integrin affinity regulation in the genetic absence of Coro1A impairs leukocyte adhesion and extravasation in inflamed cremaster muscle venules in comparison with control animals. In a Helicobacter pylori mouse infection model, PMN infiltration into the gastric mucosa is dramatically reduced in Coro1A−/− mice, resulting in an attenuated gastric inflammation. Thus, Coro1A represents an important novel player in integrin biology, with key functions in PMN trafficking during innate immunity. •Coro1A is identified as a novel regulator of β2 integrins (CD11/CD18).•Coro1A controls PMN adhesion and postadhesion events in innate immunity.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2016-11-749622