The type I macrophage scavenger receptor binds togram-positive bacteria and recognizes lipoteichoic acid.

Dunne, Dana; Resnick, David; Greenberg, J W; Krieger, Monty; Joiner, Keith A.

doi:10.1073/pnas.91.5.1863

Cited by 327 publications

(238 citation statements)

References 32 publications

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“…To determine whether the ectodomain of human CD6 and CD5 could directly bind to the surface of whole bacteria, we used an approach that was previously used for the study of SR-AI binding to bacteria (15). Thus, biotin-labeled recombinant soluble proteins encompassing the ectodomains of human CD5, CD6, and Sp␣ (rsCD5, rsCD6, and rSp␣) (Fig.…”

Section: Results Rscd6mentioning

confidence: 99%

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CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock

Sarrias

Farnós

Mota

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

101

118

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CD6 is a lymphocyte receptor that belongs to the scavenger receptor cysteine-rich superfamily. Because some members of the scavenger receptor cysteine-rich superfamily act as pattern recognition receptors for microbial components, we studied whether CD6 shares this function. We produced a recombinant form of the ectodomain of CD6 (rsCD6), which was indistinguishable (in apparent molecular mass, antibody reactivity, and cell binding properties) from a circulating form of CD6 affinity-purified from human serum. rsCD6 bound to and aggregated several Gram-positive and -negative bacterial strains through the recognition of lipoteichoic acid and LPS, respectively. The K d of the LPS-rsCD6 interaction was 2.69 ؎ 0.32 ؋ 10 ؊8 M, which is similar to that reported for the LPS-CD14 interaction. Further experiments showed that membrane CD6 also retains the LPS-binding ability, and it results in activation of the MAPK signaling cascade. In vivo experiments demonstrated that i.p. administration of rsCD6 before lethal LPS challenge significantly improved mice survival, and this was concomitant with reduced serum levels of the proinflammatory cytokines TNF-␣, IL6, and IL-1␤. In conclusion, our results illustrate the unprecedented bacterial binding properties of rsCD6 and support its therapeutic potential for the intervention of septic shock syndrome or other inflammatory diseases of infectious origin.bacterial cell component ͉ innate immunity ͉ lymphocyte surface receptor

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Section: Results Rscd6mentioning

confidence: 99%

“…Bacterial growth conditions are detailed in SI Methods. Binding of rsCD6 to bacteria was studied following a method described previously (15), with slight modifications (8).…”

Section: Expression Affinity Purification and Biotin Labeling Of Rementioning

confidence: 99%

CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock

Sarrias

Farnós

Mota

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

101

118

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“…Scavenger receptors also cooperate in the recognition of LPS and other microbial agonists. Scavenger receptor-A (SR-A) and macrophage receptor with collagen structure each bind and are regulated by LPS (16,17), and participate in microbial recognition leading to phagocytosis (16,18). Scavenger receptors may also modulate TLR4-mediated responses to LPS, since SR-A-mediated internalization of LPS leads to its degradation but does not induce cellular activation (19), and SR-A knockout mice are more sensitive to endotoxemia (20).…”

Section: Tlr Activationmentioning

confidence: 99%

Toll-Like Receptors in Health and Disease: Complex Questions Remain

Sabroe

Read

Whyte

et al. 2003

The Journal of Immunology

193

166

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“…SR recognize a diverse array of ligands that may be loosely grouped into two categories: polyanionic compounds (e.g., polyinosinic acid, fucoidan, lipotechoic acid) and modified proteins [e.g., acetylated low-density lipoprotein (AcLDL), maleylated albumin, glycated collagen] (26). Other naturally occurring ligands include polynucleotides and polysaccharides, gram-positive and gram-negative bacteria, and apoptotic cells (16,53,67). The versatile biological functions of SR include the clearance of pathological substances, host defense, cell adhesion, activation of intracellular signaling events, and cytokine production (21,26,50,51,57,65), although it is not yet clear how SR coordinate these immune and homeostatic functions.…”

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confidence: 99%

Scavenger receptor class A type I/II (CD204) null mice fail to develop fibrosis following silica exposure

Beamer¹,

Holian²

2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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Alveolar macrophages express the class A scavenger receptor (CD204) (Babaev VR, Gleaves LA, Carter KJ, Suzuki H, Kodama T, Fazio S, and Linton MF. Arterioscler Thromb Vasc Biol 20: 2593–2599, 2000); yet its role in vivo in lung defense against environmental particles has not been clearly defined. In the current study, CD204 null mice (129Sv background) were used to investigate the link between CD204 and downstream events of inflammation and fibrosis following silica exposure in vivo. CD204−/− macrophages were shown to recognize and uptake silica in vitro, although this response was attenuated compared with 129Sv wild-type mice. The production of tumor necrosis factor-α in lavage fluid was significantly enhanced in CD204 null mice compared with wild-type mice following silica exposure. Moreover, after exposure to environmental particles, CD204−/− macrophages exhibited improved cell viability in a dose-dependent manner compared with wild-type macrophages. Finally, histopathology from a murine model of chronic silicosis in 129Sv wild-type mice displayed typical focal lesions, interstitial thickening with increased connective tissue matrix, and cellular infiltrate into air space. In contrast, CD204−/− mice exhibited little to no deposition of collagen, yet they demonstrated enhanced accumulation of inflammatory cells largely composed of neutrophils. Our findings point to an important role of CD204 in mounting an efficient and appropriately regulated immune response against inhaled particles. Furthermore, these results indicate that the functions of CD204 are critical to the development of fibrosis and the resolution of inflammation.

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The type I macrophage scavenger receptor binds togram-positive bacteria and recognizes lipoteichoic acid.

Abstract: Macrophage scavenger receptors exhibit unusually broad binding specificity for polyanionic ligands and have been implicated in atherosclerosis and various host defense functions. Using a radiolabeled, secreted form of the type

Cited by 327 publications

References 32 publications

CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock

CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock

Toll-Like Receptors in Health and Disease: Complex Questions Remain

Scavenger receptor class A type I/II (CD204) null mice fail to develop fibrosis following silica exposure

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