Absence of Platelet Endothelial Cell Adhesion Molecule-1 (CD31) Leads to Increased Severity of Local and Systemic IgE-Mediated Anaphylaxis and Modulation of Mast Cell Activation

Wong, Mae-Xhum; Roberts, Donna; Bartley, Paul C.; Jackson, Denise E.

doi:10.4049/jimmunol.168.12.6455

Cited by 48 publications

(35 citation statements)

References 37 publications

(38 reference statements)

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“…As PECAM-1 Ϫ/Ϫ mice age, they develop an autoimmune lupus-like syndrome and exhibit adverse prognoses in conditions such as collagen-induced arthritis, LPS-induced septic shock, encephalomyelitis, [36][37][38][39] and endothelial X-ray irradiation, 40 demonstrating that PECAM-1 Ϫ/Ϫ mice manifest a consistent defective response to stress.…”

Section: Discussionmentioning

confidence: 99%

A novel role for PECAM-1 in megakaryocytokinesis and recovery of platelet counts in thrombocytopenic mice

Dhanjal

Pendaries

Ross

et al. 2007

Blood

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During thrombopoiesis, maturing megakaryocytes (MKs) migrate within the complex bone marrow stromal microenvironment from the proliferative osteoblastic niche to the capillary-rich vascular niche where proplatelet formation and platelet release occurs. This physiologic process involves proliferation, differentiation, migration, and maturation of MKs before platelet production occurs. In this study, we report a role for the glycoprotein PECAM-1 in thrombopoiesis. We show that following induced thrombocytopenia, recovery of the peripheral platelet count is impaired in PECAM-1-deficient mice. Whereas MK maturation, proplatelet formation, and platelet production under in vitro conditions were unaffected, we identified a migration defect in PECAM-1-deficient MKs in response to a gradient of stromal cell-derived factor 1 (SDF1), a major chemokine regulating MK migration within the bone marrow. This defect could be explained by defective PECAM-1 ؊/؊ MK polarization of the SDF1 receptor CXCR4 and an increase in adhesion to immobilized bone marrow matrix proteins that can be ex- IntroductionMegakaryocytopoiesis involves proliferation and differentiation of megakaryocyte (MK) progenitors to a large, terminally differentiated cell with a multi-lobulated, polyploid nucleus. Nuclear maturation, a process known as endoreplication, proceeds in concert with cytoplasmic maturation and expression of platelet surface markers including the glycoprotein receptors IIb/IIIa, GPIb, GPIX, and GPVI. As the MK matures and differentiates, it migrates to sinusoidal bone marrow endothelial cells where it forms transendothelial projections called proplatelets that release 1000 to 5000 platelets per MK into the intravascular space. [1][2][3][4][5] Thrombopoietin (TPO) participates in the humoral regulation of thrombopoiesis. TPO is produced constitutively in the liver and by bone marrow stromal cells and its levels are regulated by binding to the receptor c-Mpl expressed on platelets. 6 This has the net effect of reducing the concentration of TPO in the circulation and thereby inhibiting differentiation of progenitor cells along the MK lineage. Thus, megakaryocytopoiesis and platelet count are directly regulated by circulating TPO. 2 A key step in thrombopoiesis is migration of maturing MKs from the proliferative osteoblastic niche within the bone marrow microenvironment, where hematopoietic stem cells reside, to the capillary-rich vascular niche, where proplatelets are formed. 6 This process is regulated by a variety of chemokines and cytokines, as well as by adhesive interactions with interstitial cells and extracellular matrix proteins. For example, the chemokine SDF1 directs movement of MK progenitors through its receptor CXCR4 from the proliferative "osteoblastic niche" to the "vascular niche," where platelets are formed. 6 SDF1 therefore acts in combination with TPO to promote differentiation of MK progenitor cells to mature MKs. 7,8 In addition, SDF1 promotes the interaction and transmigration of mature MKs through bone marrow endothel...

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Section: Discussionmentioning

confidence: 99%

A novel role for PECAM-1 in megakaryocytokinesis and recovery of platelet counts in thrombocytopenic mice

Dhanjal

Pendaries

Ross

et al. 2007

Blood

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“…PECAM-1 promotes inflammation by facilitating leukocyte transendothelial migration (Muller et al, 1993;Vaporciyan et al, 1993;Wakelin et al, 1996) and by serving as a mechanosensor for fluid shear stress (Tzima et al, 2005), but dampens inflammation via its ability to: (1) inhibit cellular activation (Falati et al, 2006;Newman et al, 2001;Newton-Nash and Newman, 1999;Patil et al, 2001;Rui et al, 2007;Wilkinson et al, 2002;Wong et al, 2002); (2) reduce proinflammatory cytokine levels (Carrithers et al, 2005;Goel et al, 2007;Maas et al, 2005;Tada et al, 2003); (3) decrease leukocyte accumulation at sites of inflammation (Carrithers et al, 2005;Goel et al, 2007;Goel et al, 2008;Maas et al, 2005;Tada et al, 2003); and (4) maintain and restore vascular integrity (Biswas et al, 2006;Carrithers et al, 2005;Ferrero et al, 1995;Graesser et al, 2002;Maas et al, 2005). Consequently, elucidating the mechanisms by which PECAM-1 mediates both its pro-and anti-inflammatory effects has the potential to improve our understanding of how cells and tissues integrate these seemingly opposing biological signals.…”

Section: Discussionmentioning

confidence: 99%

Relative contribution of PECAM-1 adhesion and signaling to the maintenance of vascular integrity

Privratsky

Paddock

Florey

et al. 2011

Journal of Cell Science

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SummaryPECAM-1 (CD31) is a cellular adhesion and signaling receptor that is highly expressed at endothelial cell-cell junctions in confluent vascular beds. Previous studies have implicated PECAM-1 in the maintenance of vascular barrier integrity; however, the mechanisms behind PECAM-1-mediated barrier protection are still poorly understood. The goal of the present study, therefore, was to examine the pertinent biological properties of PECAM-1 (i.e. adhesion and/or signaling) that allow it to support barrier integrity. We found that, compared with PECAM-1-deficient endothelial cells, PECAM-1-expressing endothelial cell monolayers exhibit increased steady-state barrier function, as well as more rapid restoration of barrier integrity following thrombin-induced perturbation of the endothelial cell monolayer. The majority of PECAM-1-mediated barrier protection was found to be due to the ability of PECAM-1 to interact homophilically and become localized to cell-cell junctions, because a homophilic binding-crippled mutant form of PECAM-1 was unable to support efficient barrier function when re-expressed in cells. By contrast, cells expressing PECAM-1 variants lacking residues known to be involved in PECAM-1-mediated signal transduction exhibited normal to near-normal barrier integrity. Taken together, these studies suggest that PECAM-1-PECAM-1 homophilic interactions are more important than its signaling function for maintaining the integrity of endothelial cell junctions.

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“…85 Using models of experimental allergic encephalomyelitis (EAE), although an anti-PECAM-1 mAb was found not to effect disease on-set or the severity of clinical symptoms in rats, 86 PECAM-1-deficient mice exhibited early on-set of clinical symptoms and leukocyte infiltration during EAE. 82 Furthermore, enhanced CNS permeability was noted in the PECAM-1-deficient mice during the development of EAE, a response that may be associated with an impairment of vascular integrity under inflammatory conditions in these animals.…”

Section: Other Inflammatory and Vascular Disease Modelsmentioning

confidence: 99%

PECAM-1: A Multi-Functional Molecule in Inflammation and Vascular Biology

Woodfin

Voisin

Nourshargh

2007

ATVB

482

345

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Abstract-Platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) is a molecule expressed on all cells within the vascular compartment, being expressed to different degrees on most leukocyte sub-types, platelets, and on endothelial cells where its expression is largely concentrated at junctions between adjacent cells. As well as exhibiting adhesive properties, PECAM-1 is an efficient signaling molecule and is now known to have diverse roles in vascular biology including roles in angiogenesis, platelet function, and thrombosis, mechanosensing of endothelial cell response to fluid shear stress, and regulation of multiple stages of leukocyte migration through venular walls. This review will focus on some new developments with respect to the role of PECAM-1 in inflammation and vascular biology, highlighting the emerging complexities associated with the functions of this unique molecule. (Arterioscler Thromb Vasc

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Absence of Platelet Endothelial Cell Adhesion Molecule-1 (CD31) Leads to Increased Severity of Local and Systemic IgE-Mediated Anaphylaxis and Modulation of Mast Cell Activation

Cited by 48 publications

References 37 publications

A novel role for PECAM-1 in megakaryocytokinesis and recovery of platelet counts in thrombocytopenic mice

A novel role for PECAM-1 in megakaryocytokinesis and recovery of platelet counts in thrombocytopenic mice

Relative contribution of PECAM-1 adhesion and signaling to the maintenance of vascular integrity

PECAM-1: A Multi-Functional Molecule in Inflammation and Vascular Biology

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