Standardizing Scavenger Receptor Nomenclature Mercy PrabhuDas, Dawn Bowdish, Kurt Drickamer, Maria This information is current as Febbraio, Joachim Herz, Lester Kobzik, Monty Krieger, of April 20, 2014. John Loike, Terry K. Means, Soren K. Moestrup, Steven Post, Tatsuya Sawamura, Samuel Silverstein, Xiang-Yang Wang and Joseph El Khoury Downloaded from J Immunol 2014; 192:1997-2006; ; doi: 10.4049/jimmunol.1490003 http://www.jimmunol.org/content/192/5/1997 http://www.jimmunol.org/ References This article cites 76 articles, 39 of which you can access for free at: http://www.jimmunol.org/content/192/5/1997.full#ref-list-1 Subscriptions Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscriptions Permissions Submit copyright permission requests at: http://www.aai.org/ji/copyright.html at McMaster Univ Hlth Sci Lib on April 20, 2014 Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/cgi/alerts/etoc The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 9650 Rockville Pike, Bethesda, MD 20814-3994. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Standardizing Scavenger Receptor Nomenclature x Mercy PrabhuDas,* Dawn Bowdish,† Kurt Drickamer,‡ Maria Febbraio, { ‖ # †† Joachim Herz, Lester Kobzik, Montyxx Krieger, John Loike,**{{ Terry K. Means,‖‖ Soren K. Moestrup,‡‡ Steven Post, Tatsuya Sawamura, Samuel Silverstein, Xiang-Yang Wang,## and Joseph El Khoury*** Scavenger receptors constitute a large family of proteins at the workshop and to solicit additional feedback that are structurally diverse and participate in a wide from the broader research community. The Journal range of biological functions. These receptors are ex- of Immunology, 2014, 192: 1997–2006. Downloaded from pressed predominantly by myeloid cells and recognize a variety of ligands, including endogenous and modified cavenger receptor activity was first described by host-derived molecules and microbial pathogens. There Drs. Michael Brown and Joseph Goldstein when they are currently eight classes of scavenger receptors, many S identified receptors in macrophages that endocytosed of which have multiple names, leading to inconsistencies and degraded modified (acetylated), but not native, low-density http://www.jimmunol.org/ and confusion in the literature. To address this problem, lipoprotein (LDL) (1). Drs. Brown and Goldstein showed that a workshop was organized by the U.S. National Institute these acetylated LDL receptors (LDLRs) recognized a wide of Allergy and Infectious Diseases, National Institutes variety of polyanionic ligands (2). Purification and cloning of Health to help develop a clear definition of scavenger of the corresponding receptor protein and cDNA (3, 4) was receptors and a standardized nomenclature based on that soon followed by the identification of other modified LDLRs definition. Fifteen experts in the scavenger receptor field with broad binding specificity. In an initial attempt to sys- attended the workshop and, after extensive discussion, tematically categorize these receptors, Dr. Monty Krieger reached a consensus regarding the definition of scavenger proposed to subdivide them into “classes” (A, B, and so forth) receptors and a proposed scavenger receptor nomencla- based on their sequences, and each class was subdivided further at McMaster Univ Hlth Sci Lib on April 20, 2014 ture. Scavenger receptors were defined as cell surface into “types” based on additional variations in their sequences receptors that typically bind multiple ligands and pro- due to alternative splicing (5). mote the removal of non-self or altered-self targets. They There are currently eight classes of scavenger receptors often function by mechanisms that include endocytosis, (classes A–H). In some cases multiple names have been as- phagocytosis, adhesion, and signaling that ultimately signed to the same receptor (e.g., MSR1, SR-AI, CD204, lead to the elimination of degraded or harmful substances. SCARA1). Additionally, there are proteins exhibiting scav- Based on this definition, nomenclature and classification enger receptor activity that have been named based on other of these receptors into 10 classes were proposed. The criteria and have not been included in a general scavenger re- discussion and nomenclature recommendations described ceptor nomenclature. Some examples include receptor for ad- in this report only refer to mammalian scavenger recep- vanced glycation end products (RAGE), LRP1, LRP2, ASGP, tors. The purpose of this article is to describe the proposed CD163, scavenger receptor that binds phosphatidylserine and mammalian nomenclature and classification developed oxidized lipids (SR-PSOX), and CXCL16. New scavenger re- *Division of Allergy, Immunology and Transplantation, National Institute of Allergy Genetics, Institute of Molecular Medicine, Massey Cancer Center, Virginia Commonwealth and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; University School of Medicine, Richmond, VA 23298; and ***Infectious Disease Division, †Department of Pathology and Molecular Medicine, McMaster Immunology Re- Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard search Centre, M. G. DeGroote Institute of Infectious Disease Research, McMaster Medical School, Charlestown, MA 02129 University, Hamilton, Ontario L8S 4K1, Canada; ‡Department of Life Sciences, x Address correspondence and reprint requests to Dr. Mercy PrabhuDas or Dr. Joseph El Imperial College, London SW7 2AZ, United Kingdom; Department of Dentistry, Khoury, Division of Allergy, Immunology and Transplantation, National Institute of Faculty of Medicine and Dentistry, University of Alberta, Katz Group Centre for { Allergy and Infectious Diseases, National Institutes of Health, 6610 Rockledge Drive, Pharmacy and Health Research, Edmonton, Alberta T6G 2E1, Canada; Depart- Bethesda, MD 20892 (M.P.) or Infectious Disease Division, Center for Immunology ments of Molecular Genetics, Neuroscience, and Neurology and Neurotherapeutics, ‖ and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Charlestown, MA 02129 (J.E.K.). E-mail addresses: [email protected] (M.P.) Environmental Health, Harvard School of Public Health, Boston, MA 02115; #De- and [email protected] (J.E.K.) partment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; **Department of Physiology and Cellular Biophysics, Columbia University, New Abbreviations used in this article: CLEC, C-type lectin; CL-P1, collectin placenta 1; EGF, York, NY 10032; ††Center for Immunology and Inflammatory Diseases and Division epidermal growth factor; FEEL, Fasciclin, epidermal growth factor–like and lamin type of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and epidermal growth factor–like; HDL, high-density lipoprotein; Hgb, hemoglobin; LDL, Harvard Medical School, Charlestown, MA 02129; ‡‡Department of Biomedicine, low-density lipoprotein; LDLR, low-density lipoprotein receptor; LOX-1, lectin-like oxidized xx University of Aarhus, 8000 Aarhus C, Denmark; Department of Pathology, Uni- low-density lipoprotein receptor 1; MARCO, macrophage receptor with collagenous structure; {{ versity of Arkansas for Medical Sciences, Little Rock, AR 72211; Department of MEGF, multiple epidermal growth factor–like domains; RAGE, receptor for advanced gly- VascularPhysiology,ResearchInstitute,NationalCerebralandCardiovascularCen- cation end products; SRCL, scavenger receptor with C-type lectin domain; SRCR, scavenger ‖‖ ter, Suita, Osaka 565-8565, Japan; Department of Physiology and Cellular Biophys- receptor cysteine-rich; SREC, scavenger receptor expressed by endothelial cells; SR- ics, Columbia University, New York, NY 10032; ##Department of Human and Molecular PSOX, scavenger receptor that binds phosphatidylserine and oxidized lipids. www.jimmunol.org/cgi/doi/10.4049/jimmunol.1490003 1998 IMMUNOLOGY NOTES AND RESOURCES: SCAVENGER RECEPTOR NOMENCLATURE ceptors also continue to be discovered and identified (6, 7). Scavenger receptor background and history Therefore, it is important to convey consistent understanding The original description of scavenger receptors was in the and minimize redundancy and miscommunication in the scav- context of studies of lipoproteins, atherosclerosis, and familial enger receptor field. Developing a standardized nomenclature hypercholesterolemia (1, 12). Drs. Michael Brown and Joseph has the benefit of decreasing redundancy and facilitating com- Goldstein had previously identified LDLRs and LDLR- munication and collaboration among investigators within a mediated endocytosis and established that familial hypercho- field, as well as in different fields, by building on a common lesterolemia was caused by loss of function mutations in the understanding. Efforts to standardize other scientific nomen- LDLR, which led to increased plasma LDL, premature athero- clatures have occurred in areas such as chemokines and their sclerosis, and heart disease. Analysis of familial hypercholes- receptors (8), the TNF family of receptors involved in bone terolemia patients showed that plasma LDL could also be metabolism (9), complement peptide receptors (10), and glu- partially cleared by an LDLR-independent pathway called the “scavenger pathway.” The earliest use of the term “scavenger tamate receptors