Coordinated Redistribution of Leukocyte LFA-1 and Endothelial Cell ICAM-1 Accompany Neutrophil Transmigration

Shaw, Sunil K.; Ma, Shuo; Kim, Michael B.; Rao, Ravi Mohan; Hartman, Charles U.; Froio, Richard M.; Yang, Lin; Jones, Todd; Liu, Yuan; Nusrat, Asma; Parkos, Charles A.; Luscinskas, Francis W.

doi:10.1084/jem.20040965

Cited by 207 publications

(229 citation statements)

References 32 publications

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“…8 and data not shown). In contrast, mAb against JAM-A had no significant effect, as reported previously (11). The live imaging of PMN transmigration under shear stress closely resembled the studies under static conditions (Fig.…”

Section: Cd99 Plays a Role In Neutrophil Diapedesis In An In Vitro Mosupporting

confidence: 88%

“…The leukocyte moves from the site of firm adhesion to the nearest junction in a newly identified step termed locomotion, which is mediated by the ␤ 2 integrins and their counterreceptors ICAM-1 and ICAM-2 (10). Indeed, LFA-1 and ICAM-1 remain tightly apposed during the subsequent transmigration step (11). The leukocyte is then capable of transendothelial migration (TEM, transmigration, diapedesis), the movement of the leukocyte in amoeboid fashion across the interendothelial cell space and into the extracellular matrix (12,13).…”

Section: Cd99 Is a Keymentioning

confidence: 99%

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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: Cd99 Plays a Role In Neutrophil Diapedesis In An In Vitro Mosupporting

confidence: 88%

Section: Cd99 Is a Keymentioning

confidence: 99%

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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“…LFA-1 can control the rolling velocities of leukocytes in vivo, 6,16 as well as their adhesion 52 and migration 52,53 ( Figure 1). During neutrophil migration through the endothelium, LFA-1 forms ring-like clusters at the neutrophilendothelial junction.…”

Section: Integrinsmentioning

confidence: 99%

Mechanisms and Consequences of Neutrophil Interaction with the Endothelium

Zarbock

Ley

2008

The American Journal of Pathology

196

119

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Leukocyte recruitment into inflamed tissue proceeds in a cascade-like fashion. The first contact of neutrophils with the endothelium is mediated by selectins and their counterreceptors, followed by rolling of neutrophils along the endothelial wall of postcapillary venules and integrin-mediated arrest. While rolling, neutrophils collect different inflammatory signals that can activate several pathways. In addition to activation of neutrophils by ligation of G-protein-coupled receptors with chemokines and other chemoattractants, integrins and selectin ligands are also able to signal into the cell, where they initiate neutrophil extravasation, promote cytoskeletal rearrangement, and ultimately induce superoxide production and degranulation. These signaling pathways may be targeted by therapeutic interventions to inhibit specific functions of neutrophils without affecting others. This Review is focused on the signaling events during the interaction of neutrophils with the endothelium.

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“…(PECAM-1) (16,17). PECAM-1 is a constitutively expressed, abundant component of endothelial cell junctions at all levels of the vascular tree (18,19).…”

mentioning

confidence: 99%

The Neutrophil-specific Antigen CD177 Is a Counter-receptor for Platelet Endothelial Cell Adhesion Molecule-1 (CD31)

Sachs

Andrei-Selmer

Maniar

et al. 2007

Journal of Biological Chemistry

208

199

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Human neutrophil-specific CD177 (NB1 and PRV-1) has been reported to be up-regulated in a number of inflammatory settings, including bacterial infection and granulocyte-colonystimulating factor application. Little is known about its function. By flow cytometry and immunoprecipitation studies, we identified platelet endothelial cell adhesion molecule-1 (PECAM-1) as a binding partner of CD177. Real-time proteinprotein analysis using surface plasmon resonance confirmed a cation-dependent, specific interaction between CD177 and the heterophilic domains of PECAM-1. Monoclonal antibodies against CD177 and against PECAM-1 domain 6 inhibited adhesion of U937 cells stably expressing CD177 to immobilized PECAM-1. Transendothelial migration of human neutrophils was also inhibited by these antibodies. Our findings provide direct evidence that neutrophil-specific CD177 is a heterophilic binding partner of PECAM-1. This interaction may constitute a new pathway that participates in neutrophil transmigration.CD177 (NB1 and PRV-1) is a 58-to 64-kDa glycosylphosphatidylinositol-anchored glycoprotein expressed exclusively by neutrophils, neutrophilic metamyelocytes, and myelocytes, but not by any other blood cells (1, 2). We and others elucidated its primary structure by sequencing the NB1 and PRV-1 genes, which later turned out to be two alleles of a single CD177 gene (3-5). The surface expression of CD177 is unique in that only a subpopulation of neutrophils expresses this protein on the cell surface, with the mean size of the CD177-positive subpopulation ranging from 45% to 65% (2, 6).CD177 has been well studied as a target antigen in immunemediated disorders. During pregnancy, women with a CD177 null phenotype are prone to produce alloantibodies against CD177 that cross the placenta, react with fetal neutrophils, and cause neutropenia of the newborn. This mechanism let to the initial discovery of the NB1 antigen in 1971 (7). Alloantibodies to CD177, present in blood products obtained from immunized donors, have also been implicated as mediators of transfusionrelated acute lung injury (8).Although well characterized as an immunotarget, the function of CD177 is largely unknown. It has been reported that CD177 is up-regulated on the neutrophil surface upon stimulation, including during severe bacterial infections, and following granulocyte-colony-stimulating factor treatment (9). In addition, antibody-mediated clustering of CD177 primes the N-formyl-methionyl-leucyl-phenylalanine (fMLP) 3 -activated respiratory burst reaction of the neutrophil (8). Taken together, these observations make it reasonable to suppose that CD177 may be involved in processes of neutrophil-mediated host defense. One preliminary study suggests a participation of CD177 in neutrophil-endothelial cell interaction (10). The latter observation is in line with the fact that CD177, as a member of the leukocyte antigen-6 superfamily, shares a similar structure with the urokinase plasminogen activator receptor (11). Urokinase plasminogen activator receptor is expr...

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Coordinated Redistribution of Leukocyte LFA-1 and Endothelial Cell ICAM-1 Accompany Neutrophil Transmigration

Cited by 207 publications

References 32 publications

CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

Mechanisms and Consequences of Neutrophil Interaction with the Endothelium

The Neutrophil-specific Antigen CD177 Is a Counter-receptor for Platelet Endothelial Cell Adhesion Molecule-1 (CD31)

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