The collagenous domains of macrophage scavenger receptors and complement component C1q mediate their similar, but not identical, binding specificities for polyanionic ligands.

Acton, Susan; Resnick, David; Freeman, Mason W.; Ekkel, Yelena; Ashkenas, John; Krieger, Monty

doi:10.1016/s0021-9258(18)53727-3

Cited by 131 publications

(20 citation statements)

References 41 publications

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“…The ability to bind apoptotic cells and participate in clearance is a characteristic that SR-A and MARCO have in common with the structurally related complement protein C1q ( 21 ). In SLE, autoantibodies toward C1q can be found, and data suggest that they increase the severity of glomerulonephritis, but there is also the possibility that they may aff ect clearance of apoptotic cells ( 22 ).…”

Section: Class a Scavenger Receptors Are Autoantigens In Mouse And Manmentioning

confidence: 99%

Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus

Wermeling¹,

Chen

Pikkarainen

et al. 2007

The Journal of Experimental Medicine

114

100

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Apoptotic cells are considered to be a major source for autoantigens in autoimmune diseases such as systemic lupus erythematosus (SLE). In agreement with this, defective clearance of apoptotic cells has been shown to increase disease susceptibility. Still, little is known about how apoptotic cell–derived self-antigens activate autoreactive B cells and where this takes place. In this study, we find that apoptotic cells are taken up by specific scavenger receptors expressed on macrophages in the splenic marginal zone and that mice deficient in these receptors have a lower threshold for autoantibody responses. Furthermore, antibodies against scavenger receptors are found before the onset of clinical symptoms in SLE-prone mice, and they are also found in diagnosed SLE patients. Our findings describe a novel mechanism where autoantibodies toward scavenger receptors can alter the response to apoptotic cells, affect tolerance, and thus promote disease progression. Because the autoantibodies can be detected before onset of disease in mice, they could have predictive value as early indicators of SLE.

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Section: Class a Scavenger Receptors Are Autoantigens In Mouse And Manmentioning

confidence: 99%

Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus

Wermeling¹,

Chen

Pikkarainen

et al. 2007

The Journal of Experimental Medicine

114

100

View full text Add to dashboard Cite

show abstract

“…A large variety of ligands, including glycosaminoglycans, enzymes, and phospholipid vesicles, can bind to type I collagen with varying degrees of specificity. In addition, the triple-helical domain has been identified as the ligand-binding region of the macrophage scavenger receptor and the region which binds the Clq receptor [2,5,6]. Triple helices are intrinsically rod-like domains.…”

Section: Introductionmentioning

confidence: 99%

Hydration structure of a collagen peptide

1995

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“…SR-A1 is known to have an affinity for polyanionic molecules, supporting the theory that PLS is a suitable substrate . The broad specificity of SR-A1 for polyanionic substrates is due to interaction of the polyanion with cationic collagenous domains of the receptor . The binding of substrates with SR-A1 on macrophage results in internalization through clathrin-dependent and -independent processes, resulting in entry into the endosome–lysosome pathway .…”

Section: Discussionmentioning

confidence: 77%

“…39 The broad specificity of SR-A1 for polyanionic substrates is due to interaction of the polyanion with cationic collagenous domains of the receptor. 43 The binding of substrates with SR-A1 on macrophage results in internalization through clathrin-dependent and -independent processes, resulting in entry into the endosome−lysosome pathway. 39 Alternatively, SR-A1 on endothelial cells has been shown to be involved in the transcytosis of substrates.…”

Section: ■ Discussionmentioning

confidence: 99%

Application of a Scavenger Receptor A1-Targeted Polymeric Prodrug Platform for Lymphatic Drug Delivery in HIV

et al. 2020

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We have developed a macromolecular prodrug platform based on poly (L-lysine succinylated) (PLS) that targets scavenger receptor A1 (SR-A1), a receptor expressed by myeloid and endothelial cells. We demonstrate the selective uptake of PLS by murine macrophage, RAW 264.7 cells, which was eliminated upon cotreatment with the SR-A inhibitor polyinosinic acid (poly I). Further, we observed no uptake of PLS in a SR-A1-deficient RAW 264.7 cell line, even after 24 h incubation. In mice, PLS distributed to lymphatic organs following i.v. injection, as observed by ex vivo fluorescent imaging, and accumulated in lymph nodes following both i.v. or i.d. administration, based on immunohistochemical analysis with high-resolution microscopy. As a proof-of-concept, the HIV antiviral emtricitabine (FTC) was conjugated to the polymer's succinyl groups via ester bonds, with a drug loading of 14.2% (wt/wt). The prodrug (PLS-FTC) demonstrated controlled release properties in vitro with a release half-life of 15 h in human plasma and 29 h in esterase-inhibited plasma, indicating that drug release occurs through both enzymatic and non-enzymatic mechanisms. Upon incubation of PLS-FTC with human peripheral blood Supporting Information The Supporting Information is available free of charge via the Internet at http://pubs.acs.org SEC chromatograms of PLS-488 and PLS-Cy7.5; 1 H NMR spectra of PLS, partially capped PLS, fully capped PLS, FTC, 2-(2methoxyethoxy)ethanamine, and FTC; binding and uptake of PLS-488 in RAW 264.7 cells following co-treatment with partially capped PLS, fully capped PLS, poly C, or poly I; flow cytometry plots of RAW 264.7 and clone 1/2 cells following 24 h incubation with PLS-488; confocal images of PLS-488 uptake in RAW 264.7 and clone ½ cells; whole-body images of PLS-Cy7.5 treated mice; ex vivo images of organs harvested 6 h after PLS-Cy7.5 i.v. injection; IHC staining controls; standard curves of FTC with and without NaOH hydrolysis.

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The collagenous domains of macrophage scavenger receptors and complement component C1q mediate their similar, but not identical, binding specificities for polyanionic ligands.

Cited by 131 publications

References 41 publications

Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus

Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus

Hydration structure of a collagen peptide

Application of a Scavenger Receptor A1-Targeted Polymeric Prodrug Platform for Lymphatic Drug Delivery in HIV

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