More Than Just a Removal Service: Scavenger Receptors in Leukocyte Trafficking

Patten, Daniel; Shetty, Shishir

doi:10.3389/fimmu.2018.02904

Cited by 35 publications

(39 citation statements)

References 242 publications

(268 reference statements)

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“…Altogether, these findings suggest that with regard to migratory activity, loss of either LFA-1 or MAC-1 in myeloid cells may be compensated by the other β2 integrin [87]. In addition, the activity of β2 integrins as such may be dispensable in some types of infections, presumably due to partial compensation by other adhesion receptors [244][245][246]. Anyway, loss of MAC-1/CR3 on one hand may diminish pathogen clearance by phagocytic uptake [56] and also attenuate other killing mechanisms of myeloid cells [201,235].…”

Section: Metazoan Parasitesmentioning

confidence: 87%

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: Metazoan Parasitesmentioning

confidence: 87%

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

Bednarczyk

Stege

Grabbe

et al. 2020

IJMS

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“…In contrast to conventional vascular beds, the low shear flow conditions within the hepatic sinusoids leads to lack of selectin-dependent initial tethering and rolling, paving the way for atypical adhesion molecules (i.e., scavenger receptors) to play a more predominant role ( Shetty et al, 2008 ). The involvement of atypical adhesion molecules in leukocyte recruitment has been previously reviewed ( Patten and Shetty, 2018 ). Scavenger receptors are involved in recruitment of distinct leukocyte subsets, and as such, may prove to be novel liver-specific therapeutic targets ( Figure 3 ) ( Patten et al, 2019 ).…”

Section: Immunological Role Of Lsecmentioning

confidence: 99%

The Role of Sinusoidal Endothelial Cells in the Axis of Inflammation and Cancer Within the Liver

2020

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Liver sinusoidal endothelial cells (LSEC) form a unique barrier between the liver sinusoids and the underlying parenchyma, and thus play a crucial role in maintaining metabolic and immune homeostasis, as well as actively contributing to disease pathophysiology. Whilst their endocytic and scavenging function is integral for nutrient exchange and clearance of waste products, their capillarisation and dysfunction precedes fibrogenesis. Furthermore, their ability to promote immune tolerance and recruit distinct immunosuppressive leukocyte subsets can allow persistence of chronic viral infections and facilitate tumour development. In this review, we present the immunological and barrier functions of LSEC, along with their role in orchestrating fibrotic processes which precede tumourigenesis. We also summarise the role of LSEC in modulating the tumour microenvironment, and promoting development of a pre-metastatic niche, which can drive formation of secondary liver tumours. Finally, we summarise closely inter-linked disease pathways which collectively perpetuate pathogenesis, highlighting LSEC as novel targets for therapeutic intervention.

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“…Lymphocyte recruitment to the liver occurs within the specialized low flow channels of the sinusoids and via a sequential step-wise process known as the "leukocyte adhesion cascade" (10). The leukocyte adhesion cascade is mediated by a number of receptor-ligand interactions between the lymphocytes and liver sinusoidal endothelial cells (LSEC) and previous studies from our lab and others have implicated members of the scavenger receptor super-family in the recruitment of leukocytes to LSEC in vitro (11)(12)(13)(14)(15)(16). We have also shown that these endothelial-expressed scavenger receptors are present within the sinusoids of HCC tumor tissues (13,14); however, their role in shaping the tumor microenvironment via the recruitment of TILs has not been studied to date.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value and Potential Immunoregulatory Role of SCARF1 in Hepatocellular Carcinoma

et al. 2020

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Scavenger receptor class F member 1 (SCARF1) is thought to play an important role in the selective recruitment of CD4 + T cells to liver sinusoidal endothelial cells during chronic liver disease. However, the contribution of SCARF1 to hepatocellular carcinoma (HCC) is currently unknown. We utilized publically-available RNA-sequencing data from The Cancer Genome Atlas (TGCA) to explore SCARF1 expression in HCC and correlated it with a number of clinicopathological features. Flow adhesion assays were used to determine the role of SCARF1 in CD4 + T cell subset recruitment. SCARF1 expression was downregulated in HCC tumor tissues, compared to non-tumoral tissues, and loss of SCARF1 expression was associated with poorly differentiated/aggressive tumors. Additionally, higher SCARF1 expression in HCC tumor tissues was highly prognostic of better overall, disease-free and progression-free survival. SCARF1 within HCC was largely associated with tumor endothelial cells and adhesion studies suggested that it played a role in the specific recruitment of proinflammatory CD4 + T cells (CD4 + CD25 −) to HCC tumor tissues. Endothelial SCARF1 expression in tumor biopsies may provide critical prognostic information. Additionally, SCARF1 may also be a novel endothelial target that could help re-programme the microenvironment of HCC by promoting effector T cell tumor infiltration.

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More Than Just a Removal Service: Scavenger Receptors in Leukocyte Trafficking

Cited by 35 publications

References 242 publications

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

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

The Role of Sinusoidal Endothelial Cells in the Axis of Inflammation and Cancer Within the Liver

Prognostic Value and Potential Immunoregulatory Role of SCARF1 in Hepatocellular Carcinoma

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