Selectins and chemokines use shared and distinct signals to activate β2 integrins in neutrophils

Yago, Tadayuki; Zhang, Nan; Zhao, Liang; Abrams, Charles S.; McEver, Rodger P.

doi:10.1182/bloodadvances.2017015602

Cited by 42 publications

(58 citation statements)

References 58 publications

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“…54 neutrophils mediate both adhesion and signaling. 3,26,42,55 Oligomeric or immobilized P-selectin or anti-PSGL-1 antibodies can induce signals in the absence of shear stress. 56,57 Force-dependent interactions under shear stress might amplify signaling by increasing the number of P-selectin/PSGL-1 bonds or by other mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Neutrophils were isolated from bone marrow leukocytes by a density gradient method. 26 Isolation of mouse lung endothelial cells (MLECs) was performed as described previously, 27,28 with minor modifications. Briefly, lungs from 2 or 3 mice were washed, minced into 1-to 2-mm 2 pieces in 10% fetal bovine serum (FBS)-Dulbecco's modified Eagle medium (DMEM) with antibiotics, and digested with collagenase type I (2 mg/mL) at 37°C for 1 hour with occasional vortex.…”

Section: Cellsmentioning

confidence: 99%

“…Rolling of mouse bone marrow neutrophils on confluent monolayers of MLECs or on immobilized P-or E-selectin with or without coimmobilized ICAM-1 or CXCL1 was performed as described, 26 with modifications detailed in supplemental Methods. Rolling of human neutrophils on confluent monolayers of HUVECs or on immobilized human P-selectin was performed as described.…”

Section: Flow Chamber Assaymentioning

confidence: 99%

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Endothelial signaling by neutrophil-released oncostatin M enhances P-selectin–dependent inflammation and thrombosis

et al. 2019

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In the earliest phase of inflammation, histamine and other agonists rapidly mobilize P-selectin to the apical membranes of endothelial cells, where it initiates rolling adhesion of flowing neutrophils. Clustering of P-selectin in clathrin-coated pits facilitates rolling. Inflammatory cytokines typically signal by regulating gene transcription over a period of hours. We found that neutrophils rolling on P-selectin secreted the cytokine oncostatin M (OSM). The released OSM triggered signals through glycoprotein 130 (gp130)–containing receptors on endothelial cells that, within minutes, further clustered P-selectin and markedly enhanced its adhesive function. Antibodies to OSM or gp130, deletion of the gene encoding OSM in hematopoietic cells, or conditional deletion of the gene encoding gp130 in endothelial cells inhibited neutrophil rolling on P-selectin in trauma-stimulated venules of the mouse cremaster muscle. In a mouse model of P-selectin–dependent deep vein thrombosis, deletion of OSM in hematopoietic cells or of gp130 in endothelial cells markedly inhibited adhesion of neutrophils and monocytes and the rate and extent of thrombus formation. Our results reveal a paracrine-signaling mechanism by which neutrophil-released OSM rapidly influences endothelial cell function during physiological and pathological inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Cellsmentioning

confidence: 99%

Section: Flow Chamber Assaymentioning

confidence: 99%

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Endothelial signaling by neutrophil-released oncostatin M enhances P-selectin–dependent inflammation and thrombosis

et al. 2019

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“…In contrast, in the same study both Talin and Kindlin-3 were reported as essential to confer a high affinity state and migration arrest to to binding of ICAM. More recently, Yago and co-workers reported that chemokine signaling also activated both PIP5Kγ90 (phosphatidylinositol-4-phosphate 5-kinase γ90) and PI3Kγ dependent signaling which cooperated with Rap-1 to achieve an intermediate state of affinity of LFA-1 [37]. In addition, binding of PSGL-1 (P-selectin glycoprotein ligand-1) to selectins as expressed by endothelial cells activated Rap-1 and PIP5Kγ90 signaling via Src kinases as well.…”

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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“…G protein–coupled receptors on rolling neutrophils bind chemokines presented on the apical endothelium, leading to “inside-out” signals that induce conformational changes of β2-integrins ( 39 ), mediating slow rolling (low concentration) and arrest (high concentration). Chemokines synergize with selectins to activate β2-integrins when chemokine availability is limited ( 40 ). Engagement of endothelial P- or E-selectin with neutrophilic PSGL-1 triggers signals that separate LFA-1 α and β cytoplasmic tails ( 41 ), which induces integrin extension from the bent to an extended intermediate-affinity conformation ( 42 ).…”

Section: The Leukocyte Recruitment Cascade: a Paradigm Established Inmentioning

confidence: 99%

Organ-Specific Mechanisms of Transendothelial Neutrophil Migration in the Lung, Liver, Kidney, and Aorta

2018

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Immune responses are dependent on the recruitment of leukocytes to the site of inflammation. The classical leukocyte recruitment cascade, consisting of capture, rolling, arrest, adhesion, crawling, and transendothelial migration, is thoroughly studied but mostly in model systems, such as the cremasteric microcirculation. This cascade paradigm, which is widely accepted, might be applicable to many tissues, however recruitment mechanisms might substantially vary in different organs. Over the last decade, several studies shed light on organ-specific mechanisms of leukocyte recruitment. An improved awareness of this matter opens new therapeutic windows and allows targeting inflammation in a tissue-specific manner. The aim of this review is to summarize the current understanding of the leukocyte recruitment in general and how this varies in different organs. In particular we focus on neutrophils, as these are the first circulating leukocytes to reach the site of inflammation. Specifically, the recruitment mechanism in large arteries, as well as vessels in the lungs, liver, and kidney will be addressed.

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Selectins and chemokines use shared and distinct signals to activate β2 integrins in neutrophils

Abstract: Key Points Selectin and chemokine signals use both Rap1a and PIP5Kγ90 to activate β2 integrins in neutrophils. Suboptimal chemokine signals synergize with selectin signals to activate β2 integrins in neutrophils.

Cited by 42 publications

References 58 publications

Endothelial signaling by neutrophil-released oncostatin M enhances P-selectin–dependent inflammation and thrombosis

Endothelial signaling by neutrophil-released oncostatin M enhances P-selectin–dependent inflammation and thrombosis

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

Organ-Specific Mechanisms of Transendothelial Neutrophil Migration in the Lung, Liver, Kidney, and Aorta

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