P-selectin Cross-links PSGL-1 and Enhances Neutrophil Adhesion to Fibrinogen and ICAM-1 in a Src Kinase-Dependent, but GPCR-Independent Mechanism

Xu, Tao; Zhang, Lei; Geng, Zhen; Wang, Hai Bo; Wang, Liangjing; Chen, Ming; Geng, Jian Guo

doi:10.4161/cam.1.3.4984

Cited by 37 publications

(26 citation statements)

References 33 publications

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“…31 Leukocytes scanned for activated platelets to interact via P-selectin glycoprotein ligand-1 (PSGL-1) resulting in clustering and activation of the b2 integrin Mac-1 that mediates neutrophil TEM. 32,33 This simultaneous interaction with activated platelets and the endothelium results in rapid neutrophil exit and the onset of inflammation. 34 Using platelets as intermediate substrates, monocytes are able to transmigrate under high shear stress varying between 20 and 40 dyn/cm.…”

Section: Shear Forcesmentioning

confidence: 99%

Leukocyte transendothelial migration: A local affair

2016

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Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens. It serves as a protective response that involves leukocytes, blood vessels and molecular mediators with the purpose to eliminate the initial cause of cell injury and to initiate tissue repair. Inflammation is tightly regulated by the body and is associated with transient crossing of leukocytes through the blood vessel wall, a process called transendothelial migration (TEM) or diapedesis. TEM is a close collaboration between leukocytes on one hand and the endothelium on the other. Limiting vascular leakage during TEM but also when the leukocyte has crossed the endothelium is essential for maintaining vascular homeostasis. Although many details have been uncovered during the recent years, the molecular mechanisms from the vascular part that drive TEM still shows significant gaps in our understanding. This review will focus on the local signals that are induced in the endothelium that regulate leukocyte TEM and simultaneous preservation of endothelial barrier function.

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Section: Shear Forcesmentioning

confidence: 99%

Leukocyte transendothelial migration: A local affair

2016

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“…Further, studies with SFK inhibitors and isoform-specific KO mice suggested that SFKs such as Lyn and Fyn affect vWF-GPIbα binding and thus regulate platelet activation including Ca 2+ mobilization and cytoskeletal reorganization [113–115]. SFKs are also activated by the initial platelet–neutrophil attachment, and activated SFKs stabilize the cell–cell interaction [116, 117]. Studies with mice lacking double (Hck and Fgr) or triple (Hck, Fgr, and Lyn) SFKs suggested that the SFK-Pyk2 signaling axis modulates αMβ2 integrin function and thus is important for neutrophil accumulation to adherent platelets in vitro and in vivo [118].…”

Section: Molecules Regulating the Function Of Surface Receptors Requimentioning

confidence: 99%

Platelet–neutrophil interactions under thromboinflammatory conditions

Kim

Barazia

et al. 2015

Cell. Mol. Life Sci.

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Platelets primarily mediate hemostasis and thrombosis, whereas leukocytes are responsible for immune responses. Since platelets interact with leukocytes at the site of vascular injury, thrombosis and vascular inflammation are closely intertwined and occur consecutively. Recent studies using real-time imaging technology demonstrated that platelet–neutrophil interactions on the activated endothelium are an important determinant of microvascular occlusion during thromboinflammatory disease in which inflammation is coupled to thrombosis. Although the major receptors and counter receptors have been identified, it remains poorly understood how heterotypic platelet–neutrophil interactions are regulated under disease conditions. This review discusses our current understanding of the regulatory mechanisms of platelet– neutrophil interactions in thromboinflammatory disease.

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“…16 This interaction primes leukocytes for adhesion to endothelial cells by up-regulating the expression and avidity of ␤1-and ␤2 integrins on the leukocyte membrane and has been demonstrated in eosinophils, neutrophils, and monocytes. [33][34][35] To determine whether this pathway was operative in AERD, we studied the cell-specific effects of platelet adherence on the subsequent surface expression of leukocyte activation and adhesion receptors by separately gating on platelet-adherent and -nonadherent leukocyte subsets in the blood. We found especially strong up-regulation of CD18 expression in platelet-adherent monocytes (Figure 3), as well as significant increases in CD11a, CD11b, and CD11c ( Figure 3 and supplemental Figure 2), each of which partner with CD18 to form the ␤2 integrins, which permit firm adhesion of leukocytes to endothelial and epithelial cells via intracellular adhesion molecule-1 (ICAM-1).…”

Section: Platelet-wbc Adherence Causes Cyslts In Aerd 3795mentioning

confidence: 99%

Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes

Laidlaw

Kidder

Bhattacharyya

et al. 2012

Blood

218

209

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Cysteinyl leukotriene (cysLT) overproduction is a hallmark of aspirin-exacerbated respiratory disease (AERD), but its mechanism is poorly understood. Because adherent platelets can convert the leukocytederived precursor leukotriene (LT)A 4 to LTC 4 , the parent cysLT, through the terminal enzyme LTC 4 synthase, we investigated the contribution of platelet-dependent transcellular cysLT production in AERD. Nasal polyps from subjects with AERD contained many extravascular platelets that colocalized with leukocytes, and the percentages of circulating neutrophils, eosinophils, and monocytes with adherent platelets were markedly higher in the blood of subjects with AERD than in aspirintolerant controls. Platelet-adherent subsets of leukocytes had higher expression of several adhesion markers than did platelet nonadherent subsets. Adherent platelets contributed more than half of the total LTC 4 synthase activity of peripheral blood granulocytes, and they accounted for the higher level of LTC 4 generation by activated granulocytes from subjects with AERD compared with aspirintolerant controls. Urinary LTE 4 levels, a measure of systemic cysLT production, correlated strongly with percentages of circulating platelet-adherent granulocytes. Because platelet adherence to leukocytes allows for both firm adhesion to endothelial cells and augmented transcellular conversion of leukotrienes, a disturbance in plateletleukocyte interactions may be partly responsible for the respiratory tissue inflammation and the overproduction of cysLTs that characterize AERD. (Blood. 2012;119(16):3790-3798) IntroductionAspirin-exacerbated respiratory disease (AERD) is a distinctive syndrome characterized clinically by a triad of asthma, nasal polyposis, and aspirin sensitivity. It is a chronic inflammatory disease associated with eosinophilic infiltration of respiratory tissues, peripheral eosinophilia, and excessive production of cysteinyl leukotrienes (cysLTs), a class of inflammatory lipid mediators that are thought to contribute to several of the characteristic features of AERD. Individuals with this syndrome account for 4% to 11% of all adult patients with asthma, and for a disproportionate share (ϳ 30%) of patients with severe asthma. 1 The confirmatory diagnostic feature of AERD is an idiosyncratic respiratory reaction, including symptoms of acute bronchoconstriction, nasal congestion, and eye watering, on ingestion of aspirin or another nonselective cyclooxygenase (COX) inhibitor. Despite the strikingly consistent clinical phenotype of AERD, the pathogenesis of the disease remains unclear.CysLTs derive from the metabolism of arachidonic acid by effector cells of the innate immune system. In inflammatory leukocytes (neutrophils, monocytes, eosinophils, mast cells, and basophils), arachidonic acid is oxidized by 5-lipoxygenase (5-LO) to form the unstable intermediate leukotriene (LT)A 4 . 2 In neutrophils, LTA 4 is preferentially hydrolyzed by LTA 4 hydrolase to form LTB 4 , whereas in monocytes, mast cells, eosinophils, and basophils, it i...

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P-selectin Cross-links PSGL-1 and Enhances Neutrophil Adhesion to Fibrinogen and ICAM-1 in a Src Kinase-Dependent, but GPCR-Independent Mechanism

Cited by 37 publications

References 33 publications

Leukocyte transendothelial migration: A local affair

Leukocyte transendothelial migration: A local affair

Platelet–neutrophil interactions under thromboinflammatory conditions

Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes

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