Disease relevance of Cxcl16

• We investigated the role of SR-PSOX/CXCL16 on acute and adoptive experimental autoimmune encephalomyelitis (EAE), which is Th1-polarized T cell-mediated autoimmune disease of the CNS [1].
• Taken together, SR-PSOX is a novel class of molecule belonging to the scavenger receptor family, which may play important roles in pathophysiology including atherogenesis [2].
• The scavenger receptor MARCO is required for lung defense against pneumococcal pneumonia and inhaled particles [3].
• Mannose-Binding Lectin Augments the Uptake of Lipid A, Staphylococcus aureus, and Escherichia coli by Kupffer Cells through Increased Cell Surface Expression of Scavenger Receptor A [4].
• Our results do not support a critical pathogenic role for microglial SR expression in neurodegenerative alterations associated with cerebral beta amyloidosis [5].

Psychiatry related information on Cxcl16

• Microglial cells internalize aggregates of the Alzheimer's disease amyloid beta-protein via a scavenger receptor [6].

High impact information on Cxcl16

• This receptor, called scavenger receptor class B type I (SR-BI), is a fatty acylated glycoprotein that can cluster in caveolae-like domains on the surfaces of cultured cells [7].
• Ligand activation of the PPARgamma:RXRalpha heterodimer in myelomonocytic cell lines induces changes characteristic of monocytic differentiation and promotes uptake of oxLDL through transcriptional induction of the scavenger receptor CD36 [8].
• In contrast, we show it is an important regulator of the scavenger receptor CD36, which has been genetically linked to lipid accumulation in macrophages [9].
• Scavenger receptor-mediated adhesion of microglia to beta-amyloid fibrils [10].
• Scavenger-receptor ligands inhibit lipid IVA binding to, and metabolism by, RAW cells, and lipid IVA binds to type I and type II bovine scavenger receptors on transfected Chinese hamster ovary cells [11].

Chemical compound and disease context of Cxcl16

• Critical roles of CXC chemokine ligand 16/scavenger receptor that binds phosphatidylserine and oxidized lipoprotein in the pathogenesis of both acute and adoptive transfer experimental autoimmune encephalomyelitis [1].
• The class A scavenger receptor (SR-A) is a multifunctional trimeric membrane glycoprotein involved in atherogenesis [12].
• Here we show that scavenger-receptor-mediated intracellular delivery of muramyl dipeptide (MDP) to macrophages leads to efficient killing of Salmonella both in vitro and in vivo [13].
• Finally, a significant fibrate-mediated elevation (+13%; P = 0.01 compared with baseline) in the capacity of plasma from type IIB subjects to mediate free cholesterol efflux from scavenger receptor class B, type I-expressing Fu5AH hepatoma cells was observed [14].
• The experiments reveal the following pathophysiologic mechanism relevant to atherogenesis: stimulated mast cells secrete soluble heparin proteoglycans capable of forming insoluble complexes with LDL and thereby trigger uptake of LDL by macrophages through scavenger receptor-mediated phagocytosis [15].

Biological context of Cxcl16

• There was no effect on ScR mRNA abundance following LPS administration to LPS-resistant strains of mice, C3H/HeJ and IFN-gamma receptor-/-. The LPS-induced reduction in ScR mRNA in Swiss Webster mice was not sufficiently sustained to affect receptor function, as determined by the kinetics of [(125)I]-acetylated LDL clearance from plasma [16].
• Therefore, this chemokine/scavenger receptor could serve as a molecular link between lipid metabolism and immune activity in the atherosclerotic lesion [17].
• Influence of the cytocidal macrophage phenotype on the degradation of acetylated low density lipoproteins: dual regulation of scavenger receptor activity and of intracellular degradation of endocytosed ligand [18].
• Increased susceptibility of thymocytes to apoptosis in mice lacking AIM, a novel murine macrophage-derived soluble factor belonging to the scavenger receptor cysteine-rich domain superfamily [19].
• Transient transfection of the mouse macrophage cell line P388D1 with truncated scavenger receptor resulted in a 65% decrease in the uptake and degradation of Ac LDL but did not decrease the degradation of beta-migrating very low density lipoprotein, which is LDL receptor-mediated [20].

Anatomical context of Cxcl16

• All the results show that SR-PSOX/CXCL16 plays important roles in EAE by supporting generation of Ag-specific T cells, as well as recruitment of inflammatory mononuclear cells into the CNS [1].
• The scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SR-PSOX)/CXCL16 is a chemokine expressed on macrophages and dendritic cells, while its receptor expresses on T and NK T cells [1].
• Maleylated-bovine serum albumin (maleyl-BSA) elicits transcription and secretion of a number of proinflammatory genes via ligation of the low-affinity scavenger receptor (SR) on macrophages [21].
• Therefore, as observed in cultured cells, LPS administration to mice decreases ScR mRNA despite the release of several cytokines in vivo [16].
• However, LPS administration in vivo stimulates cytokine release from both macrophages and lymphocytes, the combined effects of which could alter ScR expression differently from TNF-alpha in isolation [16].

Associations of Cxcl16 with chemical compounds

• Lipopolysaccharide decreases scavenger receptor mRNA in vivo [16].
• Cloning and expression of a mouse macrophage cDNA coding for a membrane glycoprotein of the scavenger receptor cysteine-rich domain family [22].
• Viable Mtb also up-regulates inducible NO synthase, RANTES, IFN-inducible protein 10, and IRG1 in macrophages that lack mannose receptor, complement receptors 3 and 4, type A scavenger receptor, or CD40 [23].
• Scavenger receptor-specific allergen delivery elicits IFN-gamma-dominated immunity and directs established TH2-dominated responses to a nonallergic phenotype [24].
• Scavenger receptor mRNAs in rat brain microglia are induced by kainic acid lesioning and by cytokines [25].

Physical interactions of Cxcl16

• Type F scavenger receptor SREC-I interacts with advillin, a member of the gelsolin/villin family, and induces neurite-like outgrowth [26].
• Hepatic lipase may prevent such vesicular lipoproteins from accumulating in apo E-deficient mice by hydrolyzing phosphatidyl choline as scavenger receptor B1 removes the cholesteryl esters and by gradual endocytosis of lipoproteins bound to hepatic lipase on the surface of hepatocytes [27].
• Oligo-1 inhibited acetyl-LDL binding to the scavenger receptor on mouse splenocytes [28].

Enzymatic interactions of Cxcl16

• CXC chemokine ligand (CXCL)16 and scavenger receptor for phosphatidylserine and oxidized low-density lipoprotein were independently identified as a chemokine and a scavenger receptor, respectively, but have since been shown to be identical [29].
• We have demonstrated that the mesangial extracellular matrix is susceptible to metal-catalyzed oxidation and that this increases scavenger receptor-mediated adhesion of macrophages, cells which appear to be important participants in glomerular injury via their secretory products [30].

Regulatory relationships of Cxcl16

• The association of SREC-I and -II was effectively suppressed by the presence of scavenger receptor ligands such as acetylated LDL and oxidized LDL [31].
• Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene [32].
• Highly charged polyanionic ligands of the scavenger receptor trigger macrophage secretion of urokinase-type plasminogen activator (uPA) [33].
• Apolipoprotein AII enrichment of HDL enhances their affinity for class B type I scavenger receptor but inhibits specific cholesteryl ester uptake [34].
• These unique functional properties lead to the hypothesis that D6 may be involved in the control of inflammation by acting as a decoy and scavenger receptor for inflammatory chemokines [35].

Other interactions of Cxcl16

• A novel member of the class A scavenger receptor family, macrophage receptor with collagenous structure (MARCO), has recently been identified [36].
• We have cloned from murine macrophages a cDNA coding for a new protein of the scavenger receptor family whose mRNA is increased very strongly by adherence and moderately by exposure to tumor necrosis factor and interferon-gamma [22].
• Expression of other genes associated with alternative activation, including scavenger receptor A and IL-1R antagonist, is also up-regulated in MSP-stimulated murine macrophages [37].
• Inhibition of iNOS did not require the scavenger receptor or directed endocytosis and exhibited noncompetitive kinetics [38].
• Since antigens processed and presented by macrophages are known to elicit Th1 type of responses and allergic responses are characterized by polarization towards Th2 phenotype, the possibility of modulation of allergen-specific immune responses by targeting of tropomyosin to macrophage via scavenger receptor was explored [39].

Analytical, diagnostic and therapeutic context of Cxcl16

• In adoptive transfer EAE, treatment of recipient mice with anti-SR-PSOX/CXCL16 mAb also induced not only decreased clinical disease incidence, but also diminished traffic of mononuclear cells into the CNS [1].
• Molecular cloning of a novel scavenger receptor for oxidized low density lipoprotein, SR-PSOX, on macrophages [2].
• Macrophage-targeted photodynamic therapy: scavenger receptor expression and activation state [40].
• Thus, the scavenger receptor LOX-1 is certainly a promising target for cancer immunotherapy [41].
• Profiling of phospholipid species by electrospray ionization mass spectrometry showed that scavenger receptor expression led to the accumulation of phosphatidylcholine species with longer mono- or polyunsaturated acyl chains [42].

References