CD47 plays a critical role in T-cell recruitment by regulation of LFA-1 and VLA-4 integrin adhesive functions

Azcutia, Verónica; Routledge, Matthew; Williams, Marcie R.; Newton, Gail; Frazier, William A.; Manica, André; Croce, Kevin; Parkos, Charles A.; Schmider, Angela B.; Turman, Melissa V.; Soberman, Roy J.; Luscinskas, Francis W.

doi:10.1091/mbc.e13-01-0063

Cited by 60 publications

(89 citation statements)

References 39 publications

(18 reference statements)

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“…1, A, C, and D). These respective changes in leukocyte rolling and adhesion are consistent with previous reports demonstrating proinflammatory changes in the murine cremaster tissue (3,12,14,27,30). Furthermore, IL-1␤ activation induced a dramatic increase in the number of neutrophils transmigrating from venules compared with unstimulated tissues [0.5 Ϯ 0.7 and 24.3 Ϯ 8.5 events·300 m Ϫ1 ·60 min Ϫ1 in sham and IL-1␤, respectively, n ϭ 3 for both groups; Fig.…”

Section: D Intravital Imaging Of Leukocyte Tem In Vivosupporting

confidence: 91%

4D intravital microscopy uncovers critical strain differences for the roles of PECAM and CD99 in leukocyte diapedesis

Sullivan¹,

Watson²,

Müller³

2016

American Journal of Physiology-Heart and Circulatory Physiology

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Sullivan DP, Watson RL, Muller WA. 4D intravital microscopy uncovers critical strain differences for the roles of PECAM and CD99 in leukocyte diapedesis. Am J Physiol Heart Circ Physiol 311: H621-H632, 2016. First published July 15, 2016 doi:10.1152/ajpheart.00289.2016.-Leukocyte transendothelial migration (TEM) is an essential component of the inflammatory response. In vitro studies with human cells have demonstrated that platelet/endothelial cell adhesion molecule (PECAM) functions upstream of CD99 during TEM; however, results in vivo with mice have been apparently contradictory. In this study we use four-dimensional (4D) intravital microscopy to demonstrate that the site and order of function of PECAM and CD99 in vivo are dependent on the strain of mice. In FVB/n mice, PECAM functions upstream of CD99, as in human cells in vitro, and blocking antibodies against either molecule arrest neutrophils before they traverse the endothelium. However, in C57BL/6 mice, PECAM and CD99 appear to function at a different step, as the same antibodies arrest leukocyte migration through the endothelial basement membrane. These results are the first direct comparison of PECAM and CD99 function in different murine strains as well as the first demonstration of the sequential function of PECAM and CD99 in vivo.CD99; diapedesis; inflammation; intravital microscopy; platelet/endothelial cell adhesion molecule NEW & NOTEWORTHYThe data presented in this study help clarify seemingly discrepant findings in the field involving two of the common mouse strains used to study inflammation, particularly regarding the roles of PECAM and CD99 in leukocyte transendothelial migration.INFLAMMATION is part of the host's immune response to tissue damage. It involves the local delivery of leukocytes to sites of damage via a series of adhesive interactions with the endothelial cells (ECs) lining the postcapillary venules. The committed step of this process is transendothelial migration (TEM), or diapedesis, during which the leukocytes squeeze between adjacent ECs or traverse the body of an intact EC. Platelet/EC adhesion molecule (PECAM) and CD99 are two junctional adhesion molecules known to be critical for TEM (reviewed in Refs. 13 and 19). Human ECs in vitro have been used to show that PECAM functions upstream of CD99 to regulate leukocyte TEM; inhibiting PECAM function arrests leukocytes along the apical surface of the endothelium, whereas blocking CD99 arrests cells partway through EC junctions (16,23,34).In contrast to in vitro studies with human cells, in vivo studies of PECAM and CD99 in diapedesis have provided disparate results. PECAM blockade in vivo has been shown to inhibit leukocyte transmigration in all mouse strains tested except C57BL/6 mice and to arrest leukocytes along the endothelium in FVB/n mice, replicating findings in human cells in vitro. In contrast, in PECAM-deficient C57BL/6 mice, there is a transient defect in crossing the endothelial basement membrane (5, 9, 38) or no detectable effect on transmigration, depending on th...

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Section: D Intravital Imaging Of Leukocyte Tem In Vivosupporting

confidence: 91%

4D intravital microscopy uncovers critical strain differences for the roles of PECAM and CD99 in leukocyte diapedesis

Sullivan¹,

Watson²,

Müller³

2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…In contrast to the previous assay (Fig. 5), Jurkat cells were treated with 1 mM MgCl 2 and 1 mM EGTA to induce high-affinity binding of LFA-1 to ICAM-1 and thus to enhance T-lymphocyte adhesion [54,55].…”

Section: Cell Adhesion On Surfaces Presenting Gags Together With Cellmentioning

confidence: 94%

Well-defined biomimetic surfaces to characterize glycosaminoglycan-mediated interactions on the molecular, supramolecular and cellular levels

et al. 2014

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a b s t r a c tGlycosaminoglycans (GAGs) are ubiquitously present at the cell surface and in extracellular matrix, and crucial for matrix assembly, cellecell and cell-matrix interactions. The supramolecular presentation of GAG chains, along with other matrix components, is likely to be functionally important but remains challenging to control and to characterize, both in vivo and in vitro. We present a method to create welldefined biomimetic surfaces that display GAGs, either alone or together with other cell ligands, in a background that suppresses non-specific binding. Through the design of the immobilization platform e a streptavidin monolayer serves as a molecular breadboard for the attachment of various biotinylated ligands e and a set of surface-sensitive in situ analysis techniques (including quartz crystal microbalance and spectroscopic ellipsometry), the biomimetic surfaces are tailor made with tight control on biomolecular orientation, surface density and lateral mobility. Analysing the interactions between a selected GAG (heparan sulphate, HS) and the HS-binding chemokine CXCL12a (also called SDF-1a), we demonstrate that these surfaces are versatile for biomolecular and cellular interaction studies. T-lymphocytes are found to adhere specifically to surfaces presenting CXCL12a, both when reversibly bound through HS and when irreversibly immobilized on the inert surface, even in the absence of any bona fide cell adhesion ligand. Moreover, surfaces which present both HS-bound CXCL12a and the intercellular adhesion molecule 1 (ICAM-1) synergistically promote cell adhesion. Our surface biofunctionalization strategy should be broadly applicable for functional studies that require a well-defined supramolecular presentation of GAGs along with other matrix or cell-surface components.

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“…CD47 ligation also induces activation of α4β1 and αLβ2 (LFA1) integrins (Barazi et al, 2002, Azcutia et al, 2013). In sickle red blood cells CD47-dependent activation of α4β1 was associated with a cAMP-independent PKA activity that phosphorylated the cytoplasmic tail of the α4 subunit (Brittain et al, 2004).…”

Section: Downstream Signalingmentioning

confidence: 99%

CD47 signaling pathways controlling cellular differentiation and responses to stress

Soto-Pantoja

Kaur

Roberts

2015

Critical Reviews in Biochemistry and Molecular Biology

153

166

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CD47 is a widely expressed integral membrane protein that serves as the counter-receptor for the inhibitory phagocyte receptor signal-regulatory protein-α (SIRPα) and as a signaling receptor for the secreted matricellular protein thrombospondin-1. Recent studies employing mice and somatic cells lacking CD47 have revealed important pathophysiological functions of CD47 in cardiovascular homeostasis, immune regulation, resistance of cells and tissues to stress, and chronic diseases of aging including cancer. With the emergence of experimental therapeutics targeting CD47, a more thorough understanding of CD47 signal transduction is essential. CD47 lacks a substantial cytoplasmic signaling domain, but several cytoplasmic binding partners have been identified, and lateral interactions of CD47 with other membrane receptors play important roles in mediating signaling resulting from the binding of thrombospondin-1. This review addresses recent advances in identifying the lateral binding partners, signal transduction pathways, and downstream transcription networks regulated through CD47 in specific cell lineages. Major pathways regulated by CD47 signaling include calcium homeostasis, cyclic nucleotide signaling, nitric oxide and hydrogen sulfide biosynthesis and signaling, and stem cell transcription factors. These pathways and other undefined proximal mediators of CD47 signaling regulate cell death and protective autophagy responses, mitochondrial biogenesis, cell adhesion and motility, and stem cell self-renewal. Although thrombospondin-1 is the best characterized agonist of CD47, the potential roles of other members of the thrombospondin family, SIRPα and SIRPγ binding, and homotypic CD47 interactions as agonists or antagonists of signaling through CD47 should also be considered.

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CD47 plays a critical role in T-cell recruitment by regulation of LFA-1 and VLA-4 integrin adhesive functions

Abstract: CD47 plays an important but incompletely understood role in innate and adaptive immune responses. CD47 associates in cis with T-cell LFA-1 integrins and regulates expression of high-affinity conformations of both LFA-1 and VLA-4.

Cited by 60 publications

References 39 publications

4D intravital microscopy uncovers critical strain differences for the roles of PECAM and CD99 in leukocyte diapedesis

4D intravital microscopy uncovers critical strain differences for the roles of PECAM and CD99 in leukocyte diapedesis

Well-defined biomimetic surfaces to characterize glycosaminoglycan-mediated interactions on the molecular, supramolecular and cellular levels

CD47 signaling pathways controlling cellular differentiation and responses to stress

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