The Class A Macrophage Scavenger Receptor Attenuates CXC Chemokine Production and the Early Infiltration of Neutrophils in Sterile Peritonitis

Cotena, Alessia; Gordon, Siamon; Platt, Nick

doi:10.4049/jimmunol.173.10.6427

Cited by 54 publications

(47 citation statements)

References 33 publications

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“…Moreover, 129Sv and CD204Ϫ/Ϫ mice examined at 1 and 4 wk postexposure of silica showed neither differences in the accumulation of inflammatory cells nor any appreciable increase in collagen deposition in either strain of mice (data not shown), indicating that the accumulation of inflammatory cells in CD204Ϫ/Ϫ mice occurs over time. These data are consistent with a recent report demonstrating increased infiltration of neutrophils in CD204-deficient mice in response to thioglycollate peritonitis (12). It has been suggested that fibrosis begins as an inflammatory reaction with infiltration of various cell types followed by the enhanced production of cytokines (8,36).…”

Section: Discussionsupporting

confidence: 82%

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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Section: Discussionsupporting

confidence: 82%

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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“…3D), providing further support for the notion that SR expression does not promote the production of NF-kB-dependent pro-inflammatory cytokines [8,20]. Taken together, these data suggests that class A SR-deficiency results in increased production of IL-10 after LPS stimulation, adding to the evidence that these receptors affect cellular signalling pathways [21][22][23][24].Natural and induced anti-LPS IgM production is increased in class A SR-deficient mice MARCO and SR-A are constitutively expressed on peritoneal and splenic MZ macrophages, being therefore in close contact with innate B1 and MZ B-cell subsets. These two B-cell subsets are producers of natural IgM and they also rapidly produce neutralizing Ab against blood-borne bacterial and viral pathogens at early stage of infection [13,25].…”

supporting

confidence: 57%

A regulatory role for macrophage class A scavenger receptors in TLR4‐mediated LPS responses

et al. 2010

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Recognition of microbial components by TLR, key sensors of infection, leads to induction of inflammatory responses. We found that, in vivo, TLR4 engagement by LPS induces upregulation of the class A scavenger receptors (SR) macrophage receptor with a collagenous structure (MARCO) and SR-A, which occurs, at least in the case of MARCO, via both MyD88-dependent and -independent pathways. When challenging mice with a low dose of LPS followed by a high dose, class A SR-deficient mice showed a higher survival rate than WT mice. This was paired with increased production of IL-10 and anti-LPS Ab, as well as increased activation status of marginal zone B cells. However, the receptors were not crucial for survival when challenging mice i.p. with Neisseria meningitidis or Listeria monocytogenes, but they were found to contribute to microbial capture and clearance. This indicates physiological significance for the up-regulation of class A SR during early stages of bacterial infection. Thus, we believe that we have revealed a mechanism where SR regulate the activation status of the immune system and are involved in balancing a proper immune response to infection. This regulation could also be important in maintaining tolerance since these receptors have been shown to be involved in regulation of self-reactivity.Key words: Class A scavenger receptors . KO mice . LPS response . Spleen marginal zone B cells IntroductionLPS is a cell wall component of gram-negative bacteria, recognized, amongst others, by the TLR4/MD2 signalling receptor complex. Animals that have mutations in MD2 or TLR4 are susceptible to gram-negative bacterial infection due to the failure to sense LPS [1,2]. However, when animals sense LPS and respond too vigorously, they may be the victims of their own inflammatory overreaction. Therefore, the outcome of bacterial infection is determined not only by the ability to sense endotoxin, but also by mechanisms limiting the inflammatory response. Accordingly, mammals are equipped with many LPS detoxification mechanisms preventing vigorous inflammation [3]. For example, soluble proteins, such as natural Ab-binding LPS, prevent it from engaging the TLR4/MD2-complex and protect animals from endotoxin challenge [4,5]. Further, LPS can be Ã These authors contributed equally to this work. Class A SR MARCO (macrophage receptor with a collagenous structure) and SR-A (scavenger receptor A) have a potential for this type of regulation, since their ligand repertoire includes LPS and they are expressed by macrophages that respond quickly to infection. MARCO has a restricted expression pattern being expressed on specific macrophage subsets in spleen marginal zone (MZ), lymph nodes and peritoneum, whereas SR-A is more widely expressed. In vitro studies have shown that the expression of both receptors can be up-regulated in a TLR-dependent manner, suggesting that they might play a regulatory role in TLRmediated innate immune response [7,8].Being expressed primarily on MZ macrophages in the naïve spleen, MARCO and SR-A are in clos...

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“…4 and 5) resulted in enhanced expression and function of the scavenger receptor SR-A. Previous studies reported independent roles for SR-A in clearance of S. aureus and control of chemokine-driven neutrophil recruitment in the peritoneal cavity (55,56). The role of SR-A in pulmonary clearance of S. aureus is not known.…”

Section: Expression Of Sr-a Is Required For Effective Clearance and Cmentioning

confidence: 92%

“…On the other hand, the present findings show that SR-A controls neutrophil recruitment through secretion of the chemokine KC. An earlier study on sterile peritonitis revealed that SR-A regulates the rate of neutrophil chemotaxis through downmodulation of neutrophil chemokines, including KC (55). Inappropriate levels of KC during infection, however, may counteract TNF␣ priming of neutrophil bactericidal activities.…”

Section: Cd11cmentioning

confidence: 99%

Surfactant Protein A (SP-A)-mediated Clearance of Staphylococcus aureus Involves Binding of SP-A to the Staphylococcal Adhesin Eap and the Macrophage Receptors SP-A Receptor 210 and Scavenger Receptor Class A

Sever-Chroneos

Krupa

Davis

et al. 2011

Journal of Biological Chemistry

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There is limited knowledge about host factors that facilitate eradication of Staphylococcus aureus infection in the lung. Methicillin-resistant S. aureus has remained a major cause of hospital-and health care-associated pneumonia since its appearance over 40 years ago and has recently become a more prominent etiology in community acquired pneumonia. Colonization of nasal epithelium with S. aureus, a normal occurrence in over 20% of the population, increases the risk for the development of staphylococcal pneumonia (1). Furthermore, S. aureus co-infections are a major complication contributing to high morbidity and mortality during both pandemic and seasonal influenza virus pneumonia (2). S. aureus deploys a combination of virulence factors, including adhesins, toxins, and immunomodulatory molecules, that facilitate infection of different host tissues (3, 4).Surfactant protein A (SP-A) 3 is a crucial component of the pulmonary innate immune system in the alveolar spaces (5, 6). SP-A is the major protein constituent of pulmonary surfactant; it is involved in organization of large aggregate surfactant phospholipids lining the alveolar surface and acts as an opsonin for pathogens (7). SP-A is incorporated in the tubular myelin fraction of pulmonary surfactant that covers the alveolar lining fluid of the distal airway epithelium. The presence of pathogen-derived molecules may trigger reorganization of surfactant lipids (8 -11) and exposure of SP-A to bind pathogens at points of entry on the surfactant interface. Alveolar macrophages in the aqueous hypophase may then patrol areas of disturbance on the surfactant layer binding SP-A-opsonized bacteria. SP-A binds pathogens via a carboxyl-terminal carbohydrate recognition domain in a calcium-dependent manner. Amino-terminal collagen-like and coiled-coil do-

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The Class A Macrophage Scavenger Receptor Attenuates CXC Chemokine Production and the Early Infiltration of Neutrophils in Sterile Peritonitis

Cited by 54 publications

References 33 publications

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

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

A regulatory role for macrophage class A scavenger receptors in TLR4‐mediated LPS responses

Surfactant Protein A (SP-A)-mediated Clearance of Staphylococcus aureus Involves Binding of SP-A to the Staphylococcal Adhesin Eap and the Macrophage Receptors SP-A Receptor 210 and Scavenger Receptor Class A

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