TY - JOUR
T1 - Macrophage scavenger receptor a mediates adhesion to apolipoproteins A-I and E
AU - Neyen, Claudine
AU - Plüddemann, Annette
AU - Roversi, Pietro
AU - Thomas, Benjamin
AU - Cai, Lei
AU - Van Der Westhuyzen, Deneys R.
AU - Sim, Robert B.
AU - Gordon, Siamon
PY - 2009/12/22
Y1 - 2009/12/22
N2 - 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 α-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.
AB - 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 α-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.
UR - https://www.scopus.com/pages/publications/72449166872
UR - https://www.scopus.com/pages/publications/72449166872#tab=citedBy
U2 - 10.1021/bi9013769
DO - 10.1021/bi9013769
M3 - Article
C2 - 19911804
AN - SCOPUS:72449166872
SN - 0006-2960
VL - 48
SP - 11858
EP - 11871
JO - Biochemistry
JF - Biochemistry
IS - 50
ER -