title: Macrophage scavenger receptor A mediates adhesion to apolipoproteins A-I and E.
abstract: Macrophage scavenger receptor A (SR-A) is a multifunctional, multiligand pattern recognition receptor with roles in innate immunity, apoptotic cell clearance, and age-related degenerative pathologies, such as atherosclerosis and Alzheimer's disease. Known endogenous SR-A ligands are polyanionic and include modified lipoproteins, advanced glycation end products, and extracellular matrix proteins. No native plasma ligands have been identified, but it is known that SR-A recognition of unidentified serum components mediates integrin-independent macrophage adhesion, which may drive chronic local inflammation. In this study, we used a high-throughput fractionation and screening method to identify novel endogenous SR-A ligands that may mediate macrophage adhesion. SR-A was found to recognize the exchangeable apolipoproteins A-I and E (apo A-I and apo E, respectively) in both lipid-free and lipid-associated form, suggesting the shared amphipathic alpha-helix as a potential recognition motif. Adhesion of RAW 264.7 macrophages to surfaces coated with apo A-I and apo E4 proved to be integrin-independent and could be blocked by anti-SR-A antibodies. The presence of apo A-I and apo E in pathological deposits, such as atherosclerotic lesions and neurotoxic Alzheimer's plaques, suggests a possible contribution of SR-A-dependent adhesion of macrophages to an inflammatory microenvironment.
authors.affiliation: Sir William Dunn School of Pathology, Department of Biochemistry, University of Oxford,South Parks Road, Oxford OX13RE, United Kingdom.
authors.forename: Claudine
authors.initials: C
authors.lastname: Neyen
authors.forename: Annette
authors.initials: A
authors.lastname: Plüddemann
authors.forename: Pietro
authors.initials: P
authors.lastname: Roversi
authors.forename: Benjamin
authors.initials: B
authors.lastname: Thomas
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.forename: Deneys R
authors.initials: DR
authors.lastname: van der Westhuyzen
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism*; D001057:Apolipoproteins E / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D008024:Ligands; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D051117:Scavenger Receptors, Class A / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008024:Ligands; C495139:MSR1 protein, human; C495140:Msr1 protein, mouse; D051117:Scavenger Receptors, Class A