Leukocyte arrest: Biomechanics and molecular mechanisms of β 2 integrin activation

Fan, Zhichao; Ley, Klaus

doi:10.3233/bir-15085

Cited by 41 publications

(48 citation statements)

References 276 publications

(279 reference statements)

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“…Talin is necessary for unbending of the two β2 integrin subunits [33]. Kindlin-3 binds CD18 as well [34], and both Talin and Kindlin-3are required for the induction of a high affinity state of the β2 integrin [35]. Talin is necessary and sufficient to induce an intermediate state of β2 integrin affinity and to confer slow rolling of PMN on endothelium [36].…”

Section: Activation Of β2 Integrinsmentioning

confidence: 99%

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

Bednarczyk

Stege

Grabbe

et al. 2020

IJMS

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β2 integrins are heterodimeric surface receptors composed of a variable α (CD11a-CD11d) and a constant β (CD18) subunit and are specifically expressed by leukocytes. The α subunit defines the individual functional properties of the corresponding β2 integrin, but all β2 integrins show functional overlap. They mediate adhesion to other cells and to components of the extracellular matrix (ECM), orchestrate uptake of extracellular material like complement-opsonized pathogens, control cytoskeletal organization, and modulate cell signaling. This review aims to delineate the tremendous role of β2 integrins for immune functions as exemplified by the phenotype of LAD-I (leukocyte adhesion deficiency 1) patients that suffer from strong recurrent infections. These immune defects have been largely attributed to impaired migratory and phagocytic properties of polymorphonuclear granulocytes. The molecular base for this inherited disease is a functional impairment of β2 integrins due to mutations within the CD18 gene. LAD-I patients are also predisposed for autoimmune diseases. In agreement, polymorphisms within the CD11b gene have been associated with autoimmunity. Consequently, β2 integrins have received growing interest as targets in the treatment of autoimmune diseases. Moreover, β2 integrin activity on leukocytes has been implicated in tumor development.

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Section: Activation Of β2 Integrinsmentioning

confidence: 99%

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

Bednarczyk

Stege

Grabbe

et al. 2020

IJMS

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“…Similar to α4β1, the β2-integrins, also called leukocyte integrins, are indispensable for tissue immigration [27,79,89,90]. Unlike other integrins, they have only few ECM ligands since their main function is to enable adhesion to other cells through binding to members of the IgCAM superfamily, e.g., ICAMs, VCAMs or JAMs.…”

Section: β2-integrinsmentioning

confidence: 99%

The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis

Hintermann

Christen

2019

Cells

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Fibrogenesis is a progressive scarring event resulting from disrupted regular wound healing due to repeated tissue injury and can end in organ failure, like in liver cirrhosis. The protagonists in this process, either liver-resident cells or patrolling leukocytes attracted to the site of tissue damage, interact with each other by soluble factors but also by direct cell–cell contact mediated by cell adhesion molecules. Since cell adhesion molecules also support binding to the extracellular matrix, they represent excellent biosensors, which allow cells to modulate their behavior based on changes in the surrounding microenvironment. In this review, we focus on selectins, cadherins, integrins and members of the immunoglobulin superfamily of adhesion molecules as well as some non-classical cell adhesion molecules in the context of hepatic fibrosis. We describe their liver-specific contributions to leukocyte recruitment, cell differentiation and survival, matrix remodeling or angiogenesis and touch on their suitability as targets in antifibrotic therapies.

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“…These integrins, like 2 others, are heterodimeric glycoproteins that exist in four forms on the PMN. Each displays a unique α-subunit (CD11a, b, c, or d) and an identical β-subunit (CD18) 101 . The epithelial counter-receptor for PMN β2 integrins remains elusive, and functional mapping studies of this β2 integrin-dependent pathway has suggested that the profile of inhibition is distinct from that of other known ligands of CD11b/CD18 94 .…”

Section: Epithelial Endpoint Responses To Cytokinesmentioning

confidence: 99%

Cytokine responses and epithelial function in the intestinal mucosa

Onyiah

Colgan

2016

Cell. Mol. Life Sci.

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Inflammatory diseases of mucosal organs are significantly influenced by the microenvironment in which they reside. Cytokines found within this microenvironment contribute significantly to endpoint functions of the mucosa. Studies dating back to the 1990’s have revealed that epithelial cells are both a source as well as a target for numerous cytokines and that such signaling can substantially influence the outcome of mucosal disease, such as inflammatory bowel disease. Here, we will review literature regarding intestinal epithelial cells as sources and responders to cytokines found in the intestinal milieu. These studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation.

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Leukocyte arrest: Biomechanics and molecular mechanisms of β 2 integrin activation

Cited by 41 publications

References 276 publications

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis

Cytokine responses and epithelial function in the intestinal mucosa

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