DNAM-1 and PVR Regulate Monocyte Migration through Endothelial Junctions

Reymond, Nicolas; Imbert, Anne; Devilard, Élisabeth; Fabre, Stéphanie; Chabannon, Christian; Xerri, Luc; Farnarier, Catherine; Cantoni, Claudia; Bottino, Cristina; Moretta, Alessandro; Dubreuil, Patrice; Lopez, Marc

doi:10.1084/jem.20032206

Cited by 248 publications

(211 citation statements)

References 39 publications

(62 reference statements)

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“…Poliovirus receptor is a member of a related family of junctional proteins on EC and binds to CD226 on leukocytes. Blocking either poliovirus receptor or CD226 reduced monocyte TEM in an in vitro assay (46). Thus, it appears that diapedesis is regulated by a number of molecular interactions, some homophilic and some heterophilic.…”

Section: Discussionmentioning

confidence: 98%

CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

Lou

Alcaide

Luscinskas

et al. 2007

The Journal of Immunology

154

145

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Transendothelial migration of leukocytes is a critical event for inflammation, but the molecular regulation of this event is only beginning to be understood. PECAM (CD31) is a major mediator of monocyte and neutrophil transmigration, and CD99 was recently defined as a second mediator of the transmigration of monocytes. Expression of CD99 on the surface of circulating polymorphonuclear cells (PMN) is low compared with expression of CD99 on monocytes or expression of PECAM on PMN. We demonstrate here that, despite low expression of CD99, Fab of Abs against CD99 blocked over 80% of human neutrophils from transmigrating across HUVEC monolayers in an in vitro model of inflammation. Blocking CD99 on either the neutrophil or endothelial cell side resulted in a quantitatively equivalent block, suggesting a homophilic interaction between CD99 on the neutrophil and CD99 on the endothelial cell. Blocking CD99 and PECAM together resulted in additive effects, suggesting the two molecules work at distinct steps. Confocal microscopy confirmed that CD99-blocked neutrophils lodged in endothelial cell junctions at locations distal to PECAM-blocked neutrophils. The CD99-blocked PMN exhibited dynamic lateral movement within endothelial cell junctions, indicating that only the diapedesis step was blocked by interference with CD99. Anti-CD99 mAb also blocked PMN transmigration in a second in vitro model that incorporated shear stress. Taken together, the evidence demonstrates that PECAM and CD99 regulate distinct, sequential steps in the transendothelial migration of neutrophils during inflammation.

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Section: Discussionmentioning

confidence: 98%

CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

Lou

Alcaide

Luscinskas

et al. 2007

The Journal of Immunology

154

145

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“…A number of studies have shown that several JAM-like or CTX family members are expressed at intercellular junctions including nectins (Bottino et al, 2003;Reymond et al, 2004), JAMs (Martin-Padura et al, 1998;Liu et al, 2000), A33 antigen (Johnstone et al, 2000), and CARs (Bergelson et al, 1997;Carson et al, 1997;Tomko et al, 1997). Given the known adhesion properties and tissue distribution profiles of CTX family members, we initiated studies to investigate the possibility of binding interactions between junctional CTX proteins and PMN in regulating PMN transepithelial migration.…”

Section: Identification Of Epithelial Car As a Binding Partner For Jamlmentioning

confidence: 99%

Neutrophil Migration across Tight Junctions Is Mediated by Adhesive Interactions between Epithelial Coxsackie and Adenovirus Receptor and a Junctional Adhesion Molecule-like Protein on Neutrophils

Zen

Liu

McCall

et al. 2005

MBoC

159

166

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Neutrophil (polymorphonuclear leukocytes [PMN]) transepithelial migration during inflammatory episodes involves INTRODUCTIONPolymorphonuclear leukocytes (PMN) are the first line of host defense against infection by bacterial pathogens and are rapidly recruited to sites of bacterial invasion. Because the majority of pathogens are encountered at mucosal surfaces, PMN must migrate out of the circulation, through the interstitium and across the epithelium to engage offending microbes. Although migration of PMN across the epithelium in this response is a terminal event, it is vitally important since elimination of pathogens and disease pathophysiology are direct consequences of PMN transepithelial migration. Despite the importance of this terminal event in the acute inflammatory response, many of the details regarding the regulation of PMN migration across mucosal surfaces remain undefined. Studies on this have revealed that migration of PMN across epithelial barriers involves a concerted series of cell-cell interactions between the PMN and epithelial cells (Zen and Parkos, 2003;Liu et al., 2004b). There is solid evidence that initial PMN-epithelial binding requires leukocyte ␤ 2 integrins, especially CD11b/CD18 (Parkos, 1997) and that the rate of PMN migration between epithelial cells is dependent on downstream signaling events from binding interactions between epithelial CD47 and PMNexpressed signal regulatory protein ␣ . Recent studies have begun to shed light on the nature of additional receptor-ligand pairs that may regulate PMN transepithelial migration in an organ-specific manner that are distinct from processes regulating transendothelial migration.Although the leukocyte ␤ 2 integrin CD11b/CD18 is a key adhesive element that regulates PMN transepithelial migration, there is evidence that additional adhesion molecules expressed on both PMN and epithelia must participate in PMN transepithelial migration, especially at the level of epithelial intercellular junctions. Recently, certain members of a growing family of proteins termed junctional adhesion molecules (JAMs) that are intercellular junction-associated, type-I Ig superfamily proteins (IgSFs) have been shown to serve as ligands for PMN and monocytes as they migrate across endothelial (Martin-Padura et al., 1998;Del Maschio et al., 1999;Johnson-Leger et al., 2002;Ostermann et al., 2002) and epithelial monolayers (Zen et al., 2004 (Ebnet et al., 2000;Takekuni et al., 2003) or desmosomes (Zen et al., 2004). JAMs are differentially expressed on a variety of endothelia, epithelia, and leukocytes and, under specific conditions, have been shown to mediate homophilic or heterophilic binding interactions that are important in regulating epithelial/endothelial monolayer barrier function and leukocyte transmigration (Martin-Padura et al., 1998;Cunningham et al., 2000;Liu et al., 2000;Cohen et al., 2001;Johnson-Leger et al., 2002;Liang et al., 2002;Mandell et al., 2004). In addition to homophilic/heterophilic interactions among JAM proteins, two family members, JAM-A ...

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“…The b 2 -integrin LFA-1 (CD11a/CD18), the poliovirus receptor (PVR/CD155) and PVR-related family-2 receptor (PRR-2/CD112) have been identified as ligands for CD226. 21 Interaction of CD226 with PVR has a role in endothelial transmigration of leukocytes, 22 and anti-CD226 treatment leads to delayed onset and an attenuated disease course in a mouse model of MS. 21 A profound alteration of the T-cell response including Th1 and Th17 responses, natural-killer-likeT-cells anomalously expressing natural killer-receptors, and dysfunctional regulatory T-cells is observed in WG. [23][24][25][26] Thus, similar to T1D, MS and rheumatoid arthritis, in which distinct T-cell alterations are also common, CD226 polymorphisms could predispose to the altered T-cell response in WG.…”

mentioning

confidence: 99%