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  • Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation.

Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation.

Immunity (2021-08-08)
Natalia Reglero-Real, Lorena Pérez-Gutiérrez, Azumi Yoshimura, Loïc Rolas, José Garrido-Mesa, Anna Barkaway, Catherine Pickworth, Rebeca S Saleeb, Maria Gonzalez-Nuñez, Shani N Austin-Williams, Dianne Cooper, Laura Vázquez-Martínez, Tao Fu, Giulia De Rossi, Matthew Golding, Mathieu-Benoit Voisin, Chantal M Boulanger, Yoshiaki Kubota, William A Muller, Sharon A Tooze, Thomas D Nightingale, Lucy Collinson, Mauro Perretti, Ezra Aksoy, Sussan Nourshargh
ABSTRACT

The migration of neutrophils from the blood circulation to sites of infection or injury is a key immune response and requires the breaching of endothelial cells (ECs) that line the inner aspect of blood vessels. Unregulated neutrophil transendothelial cell migration (TEM) is pathogenic, but the molecular basis of its physiological termination remains unknown. Here, we demonstrated that ECs of venules in inflamed tissues exhibited a robust autophagic response that was aligned temporally with the peak of neutrophil trafficking and was strictly localized to EC contacts. Genetic ablation of EC autophagy led to excessive neutrophil TEM and uncontrolled leukocyte migration in murine inflammatory models, while pharmacological induction of autophagy suppressed neutrophil infiltration into tissues. Mechanistically, autophagy regulated the remodeling of EC junctions and expression of key EC adhesion molecules, facilitating their intracellular trafficking and degradation. Collectively, we have identified autophagy as a modulator of EC leukocyte trafficking machinery aimed at terminating physiological inflammation.

MATERIALS
Product Number
Brand
Product Description

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Bovine Serum Albumin, heat shock fraction, low endotoxin, pH 7, ≥98%
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Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-15, ascites fluid
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Endothelial cell growth supplement from bovine neural tissue, ECGS, suitable for cell culture
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Zymosan A from Saccharomyces cerevisiae, for inducing inflamatory response
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Paraformaldehyde, powder, 95%
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Heparin sodium salt from porcine intestinal mucosa, Grade I-A, ≥180 USP units/mg
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Tyrode′s Solution, Acidic, liquid, sterile-filtered, suitable for mouse embryo cell culture
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Propidium iodide solution
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Fetal Bovine Serum, Heat Inactivated, non-USA origin, sterile-filtered, suitable for cell culture
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Ethylenediaminetetraacetic acid, anhydrous, BioUltra, ≥99% (titration)