Endothelial CD47 promotes vascular endothelial-cadherin tyrosine phosphorylation and participates in T cell recruitment at sites of inflammation in vivo

The Journal of Immunology : Official Journal of the American Association of Immunologists
Verónica AzcutiaFrancis W Luscinskas

Abstract

At sites of inflammation, endothelial adhesion molecules bind leukocytes and transmit signals required for transendothelial migration (TEM). We previously reported that adhesive interactions between endothelial cell CD47 and leukocyte signal regulatory protein γ (SIRPγ) regulate human T cell TEM. The role of endothelial CD47 in T cell TEM in vivo, however, has not been explored. In this study, CD47⁻/⁻ mice showed reduced recruitment of blood T cells as well as neutrophils and monocytes in a dermal air pouch model of TNF-α-induced inflammation. Reconstitution of CD47⁻/⁻ mice with wild-type bone marrow cells did not restore leukocyte recruitment to the air pouch, indicating a role for endothelial CD47. The defect in leukocyte TEM in the CD47⁻/⁻ endothelium was corroborated by intravital microscopy of inflamed cremaster muscle microcirculation in bone marrow chimera mice. In an in vitro human system, CD47 on both HUVEC and T cells was required for TEM. Although previous studies showed CD47-dependent signaling required G(αi)-coupled pathways, this was not the case for endothelial CD47 because pertussis toxin, which inactivates G(αi), had no inhibitory effect, whereas G(αi) was required by the T cell for TEM. We next investigated th...Continue Reading

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Citations

Jan 25, 2013·Veterinary Pathology·W A Muller
Sep 6, 2013·Molecular Biology of the Cell·Veronica AzcutiaFrancis W Luscinskas
Oct 17, 2015·Nature Reviews. Immunology·Dietmar Vestweber
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Feb 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Neva B WatsonPaul T Massa
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Jan 11, 2020·Frontiers in Immunology·Elena Martin-OrozcoMaria Ayala-San Nicolas
Jun 20, 2020·Immunity, Inflammation and Disease·Liliya K DobrodeevaSvetlana N Balashova
Jun 8, 2021·Frontiers in Immunology·Yoko OkunukiKip M Connor

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