Understanding Molecules that Mediate Leukocyte Extravasation

Rutledge, Nakisha S.; Müller, William A.

doi:10.1007/s40139-020-00207-9

Cited by 10 publications

(7 citation statements)

References 103 publications

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“…Leukocyte arrest and migration on the endothelium depends on chemokines ( Luu et al, 2000 ). The shift from fast rolling to slow rolling allows G-protein-coupled receptors (GPCRs) on leukocytes to bind to the chemokines expressed on the surface of ECs, which induces leukocyte integrin activation and enables leukocyte firm adhesion to the vessel wall ( Giagulli et al, 2004 ; Rutledge and Muller, 2020 ). Integrins are a family of transmembrane receptors expressed by leukocytes.…”

Section: The Molecular Processes Of Leukocyte Recruitment In Inflammamentioning

confidence: 99%

“…Conformational changes are required for integrins to switch from a low affinity state to an active high affinity state enabling them to bind to their ligands expressed on the endothelium ( Kim et al, 2003 ; Ley et al, 2007 ; Fan and Ley, 2015 ). The activation of integrins is mediated by chemokines and results in integrin extension and changes in the cytoskeleton of leukocytes, enabling tight adhesion on the vessel wall ( Rutledge and Muller, 2020 ). LFA-1 and VLA-4 on leukocytes, bind to their respective ligand ICAM-1 and VCAM-1 on ECs, mediate leukocyte adhesion ( Hyduk et al, 2007 ; Kuwano et al, 2010 ) and induce intracellular signals to allow leukocyte arrest ( Giagulli et al, 2006 ; Kummer and Ebnet, 2018 ).…”

Section: The Molecular Processes Of Leukocyte Recruitment In Inflammamentioning

confidence: 99%

“…LFA-1 and VLA-4 on leukocytes, bind to their respective ligand ICAM-1 and VCAM-1 on ECs, mediate leukocyte adhesion ( Hyduk et al, 2007 ; Kuwano et al, 2010 ) and induce intracellular signals to allow leukocyte arrest ( Giagulli et al, 2006 ; Kummer and Ebnet, 2018 ). Leukocytes then extend lamellipodia and prepare for transendothelial migration ( Rutledge and Muller, 2020 ). Additional downstream signals such as prostaglandin-D2 (PGD2) signals are required for shape change and dynamic transmigration of activated leukocytes ( Ahmed et al, 2011 ).…”

Section: The Molecular Processes Of Leukocyte Recruitment In Inflammamentioning

confidence: 99%

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Dysregulation of Leukocyte Trafficking in Type 2 Diabetes: Mechanisms and Potential Therapeutic Avenues

Pezhman

Tahrani

Chimen

2021

Front. Cell Dev. Biol.

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Type 2 Diabetes Mellitus (T2DM) is a chronic inflammatory disorder that is characterized by chronic hyperglycemia and impaired insulin signaling which in addition to be caused by common metabolic dysregulations, have also been associated to changes in various immune cell number, function and activation phenotype. Obesity plays a central role in the development of T2DM. The inflammation originating from obese adipose tissue develops systemically and contributes to insulin resistance, beta cell dysfunction and hyperglycemia. Hyperglycemia can also contribute to chronic, low-grade inflammation resulting in compromised immune function. In this review, we explore how the trafficking of innate and adaptive immune cells under inflammatory condition is dysregulated in T2DM. We particularly highlight the obesity-related accumulation of leukocytes in the adipose tissue leading to insulin resistance and beta-cell dysfunction and resulting in hyperglycemia and consequent changes of adhesion and migratory behavior of leukocytes in different vascular beds. Thus, here we discuss how potential therapeutic targeting of leukocyte trafficking could be an efficient way to control inflammation as well as diabetes and its vascular complications.

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Section: The Molecular Processes Of Leukocyte Recruitment In Inflammamentioning

confidence: 99%

Section: The Molecular Processes Of Leukocyte Recruitment In Inflammamentioning

confidence: 99%

Section: The Molecular Processes Of Leukocyte Recruitment In Inflammamentioning

confidence: 99%

See 1 more Smart Citation

Dysregulation of Leukocyte Trafficking in Type 2 Diabetes: Mechanisms and Potential Therapeutic Avenues

Pezhman

Tahrani

Chimen

2021

Front. Cell Dev. Biol.

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“…44,83 Leukocyte adhesion during extravasation is mediated by complex interactions between the leucocyte molecules very late antigen-4, lymphocyte functionassociated antigen 1, Mac-1, CR3, platelet endothelial cell adhesion molecule 1 and CD99 and their endothelial cell counter ligands vascular cell adhesion molecule-1, intercellular adhesion molecule-1/2, platelet endothelial cell adhesion molecule 1 and CD99. 84 Binding of integrins present on the leukocytes to the vascular endothelial adhesion molecules such as intercellular adhesion molecule exerts mechanical forces on integrins, which are then translated to signaling pathways regulating actin cytoskeleton remodeling and the generation of traction forces in leukocytes. These processes in turn enable leukocytes to change their shape from sphere-like to elongated and flattened, thereby enhancing efficient adhesion, spreading and crawling.…”

Section: Inflammatory Effects Of Membrane-bound and Proteolytically C...mentioning

confidence: 99%

Soluble vascular endothelial glycocalyx proteoglycans as potential therapeutic targets in inflammatory diseases

Kunnathattil,

Rahul,

Skaria

2023

Immunol Cell Biol

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Reducing the activity of cytokines and leukocyte extravasation is an emerging therapeutic strategy to limit tissue‐damaging inflammatory responses and restore immune homeostasis in inflammatory diseases. Proteoglycans embedded in the vascular endothelial glycocalyx, which regulate the activity of cytokines to restrict the inflammatory response in physiological conditions, are proteolytically cleaved in inflammatory diseases. Here we critically review the potential of proteolytically shed, soluble vascular endothelial glycocalyx proteoglycans to modulate pathological inflammatory responses. Soluble forms of the proteoglycans syndecan‐1, syndecan‐3 and biglycan exert beneficial anti‐inflammatory effects by the removal of chemokines, suppression of proinflammatory cytokine expression and leukocyte migration, and induction of autophagy of proinflammatory M1 macrophages. By contrast, soluble versikine and decorin enhance proinflammatory responses by increasing inflammatory cytokine synthesis and leukocyte migration. Endogenous syndecan‐2 and mimecan exert proinflammatory effects, syndecan‐4 and perlecan mediate beneficial anti‐inflammatory effects and glypican regulates Hh and Wnt signaling pathways involved in systemic inflammatory responses. Taken together, targeting the vascular endothelial glycocalyx–derived, soluble syndecan‐1, syndecan‐2, syndecan‐3, syndecan‐4, biglycan, versikine, mimecan, perlecan, glypican and decorin might be a potential therapeutic strategy to suppress overstimulated cytokine and leukocyte responses in inflammatory diseases.

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“…Integrins are known to play an important role in leukocyte extravasation from the periphery into inflamed tissues ( 83 ). Leukocyte integrins can interact with endothelium VCAMs and ICAMs to lock the leukocyte onto the endothelium and permit diapedesis ( 83 , 84 ). The loss of functional β2 integrins impedes leukocyte migration as highlighted in genetic leukocyte adhesion deficiencies (LAD) I and III.…”

Section: Cd11d Impact On Leukocyte Migrationmentioning

confidence: 99%

β2 Integrin CD11d/CD18: From Expression to an Emerging Role in Staged Leukocyte Migration

et al. 2021

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CD11d/CD18 is the most recently discovered and least understood β2 integrin. Known CD11d adhesive mechanisms contribute to both extravasation and mesenchymal migration – two key aspects for localizing peripheral leukocytes to sites of inflammation. Differential expression of CD11d induces differences in monocyte/macrophage mesenchymal migration including impacts on macrophage sub-set migration. The participation of CD11d/CD18 in leukocyte localization during atherosclerosis and following neurotrauma has sparked interest in the development of CD11d-targeted therapeutic agents. Whereas the adhesive properties of CD11d have undergone investigation, the signalling pathways induced by ligand binding remain largely undefined. Underlining each adhesive and signalling function, CD11d is under unique transcriptional control and expressed on a sub-set of predominately tissue-differentiated innate leukocytes. The following review is the first to capture the nearly three decades of CD11d research and discusses the emerging role of CD11d in leukocyte migration and retention during the progression of a staged immune response.

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Understanding Molecules that Mediate Leukocyte Extravasation

Cited by 10 publications

References 103 publications

Dysregulation of Leukocyte Trafficking in Type 2 Diabetes: Mechanisms and Potential Therapeutic Avenues

Dysregulation of Leukocyte Trafficking in Type 2 Diabetes: Mechanisms and Potential Therapeutic Avenues

Soluble vascular endothelial glycocalyx proteoglycans as potential therapeutic targets in inflammatory diseases

β2 Integrin CD11d/CD18: From Expression to an Emerging Role in Staged Leukocyte Migration

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