Leukocyte–endothelial-cell interactions in leukocyte transmigration and the inflammatory response

Müller, William A.

doi:10.1016/s1471-4906(03)00117-0

Cited by 679 publications

(662 citation statements)

References 75 publications

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“…The increase in JAM-1 may be an adaptive response to the earlier claudin-5 decrease and subsequent loss of barrier function. It is also possible that the increase in JAM-1 expression is related to the CFA-induced increase in circulating neutrophils, as JAM-1 is involved in leukocyte diapedesis (Muller, 2003). As the CFAinduced inflammatory hyperalgesia continues, paracellular permeability is again increased, where at 72 h, we described an 81% increase in sucrose paracellular permeability across the BBB.…”

Section: Discussionmentioning

confidence: 70%

Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

et al. 2006

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The blood-brain barrier (BBB) is a dynamic system which maintains brain homeostasis and limits CNS penetration via interactions of transmembrane and intracellular proteins. Inflammatory pain (IP) is a condition underlying several diseases with known BBB perturbations, including stroke, Parkinson's, multiple sclerosis and Alzheimer's. Exploring the underlying pathology of chronic IP, we demonstrated alterations in BBB paracellular permeability with correlating changes in tight junction (TJ) proteins: occludin and claudin-5. The present study examines the IP-induced molecular changes leading to a loss in functional BBB integrity. IP was induced by injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the right hindpaw of female Sprague-Dawley rats. Inflammation and hyperalgesia were confirmed, and BBB paracellular permeability was assessed by in situ brain perfusion of [ 14 C]sucrose (paracellular diffusion marker). The permeability of the BBB was significantly increased at 24 and 72 h post-CFA. Analysis of the TJ proteins, which control the paracellular pathway, demonstrated decreased claudin-5 expression at 24 h, and an increase at 48 and 72 h post-injection. Occludin expression was significantly decreased 72 h post-CFA. Expression of junction adhesion molecule-1 (JAM-1) increased 48 h and decreased by 72 h post-CFA. Confocal microscopy demonstrated continuous expression of both occludin and JAM-1, each co-localizing with ZO-1. The increased claudin-5 expression was not limited to the junction. These results provide evidence that chronic IP causes dramatic alterations in specific cytoarchitectural proteins and demonstrate alterations in molecular properties during CFA, resulting in significant changes in BBB paracellular permeability.

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Section: Discussionmentioning

confidence: 70%

Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

et al. 2006

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“…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). Transmigration is largely an irreversible process for neutrophils and commits these cells to enter the inflammatory site.…”

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

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157

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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“…Outside of structurally organized junctional complexes, the transmembrane protein platelet/endothelial cell adhesion molecule (PECAM)-1 is concentrated at the endothelial cell contacts. Nevertheless, PECAM-1 has also been shown to mediate diapedesis of leukocytes across the vascular endothelium [18].…”

Section: Introductionmentioning

confidence: 99%

Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node

et al. 2008

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Lymph nodes are strategically localized at the interfaces between the blood and lymphatic vascular system, delivering immune cells and antigens to the lymph node. As cellular junctions of endothelial cells actively regulate vascular permeability and cell traffic, we have investigated their molecular composition by performing an extensive immunofluorescence study for adherens and tight junction molecules, including vascular endothelium (VE)-cadherin, the vascular claudins 1, 3, 5 and 12, occludin, members of the junctional adhesion molecule family plus endothelial cell-selective adhesion molecule (ESAM)-1, platelet endothelial cell adhesion molecule-1, ZO-1 and ZO-2. We found that junctions of high endothelial venules (HEV), which serve as entry site for naive lymphocytes, are unique due to their lack of the endothelial cell-specific claudin-5. LYVE-1 + sinus-lining endothelial cells form a diffusion barrier for soluble molecules that arrive at the afferent lymph and use claudin-5 and ESAM-1 to establish characteristic tight junctions. Analysis of the spatial relationship between the different vascular compartments revealed that HEV extend beyond the paracortex into the medullary sinuses, where they are protected from direct contact with the lymph by sinus-lining endothelial cells. The specific molecular architecture of cellular junctions present in blood and lymphatic vessel endothelium in peripheral lymph nodes establishes distinct barriers controlling the distribution of antigens and immune cells within this tissue.

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Leukocyte–endothelial-cell interactions in leukocyte transmigration and the inflammatory response

Cited by 679 publications

References 75 publications

Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node

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