Abstract
Asamacrophage-restrictedreagent, the generation and application of the F4/80 mAb has greatly benefited the phenotypic characterization of mouse tissue macrophages for three decades. Following the molecular identification of the F4/80 antigen as an EGF-TM7 member of the adhesion-GPCR family, great interest was ignited to understand its cell type-specific expression pattern as well as its functional role in macrophage biology. Recent studies have shown that the F4/80 gene is regulated by a novel set of transcription factors that recognized a unique promoter sequence. Gene targeting experiments have produced two F4/80 knock out animal models and showed that F4/80 isnotrequired for normal macrophage development. Nevertheless, the F4/80 receptor was found to be necessary for the induction of efferent CD8+ regulatory T cells responsible for peripheral immune tolerance. The identification of cellular ligands for F4/80 and delineation of its signaling pathway remain elusive but are critical to understand the in vivo role of this macrophage-specific adhesion-GPCR.
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References
Taylor PR, Martinez-Pomares L, Stacey M et al. Macrophage receptors and immune recognition. Annu Rev Immunol 2005; 23:901–944.
Martinez-Pomares L, Platt N, McKnight AJ et al. Macrophage membrane molecules: markers of tissue differentiation and heterogeneity. Immunobiology 1996; 195(4-5):407–416.
McKnight AJ, Gordon S. Membrane molecules as differentiation antigens of murine macrophages. Adv Immunol 1998; 68:271–314.
Austyn JM, Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol 1981; 11(10):805–815.
Starkey PM, Turley L, Gordon S. The mouse macrophage-specific glycoprotein defined by monoclonal antibody F4/80: characterization, biosynthesis and demonstration of a rat analogue. Immunology 1987; 60(1):117–122.
Lin HH, Stubbs LJ, Mucenski ML. Identification and characterization of a seven transmembrane hormone receptor using differential display. Genomics 1997; 41(3):301–308.
McKnight AJ, Macfarlane AJ, Dri P et al. Molecular cloning of F4/80, a murine macrophage-restricted cell surface glycoprotein with homology to the G-protein-linked transmembrane 7 hormone receptor family. J Biol Chem 1996;271(1):486–489.
Lin HH, Faunce DE, Stacey M et al. The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T-cells in peripheral tolerance. J Exp Med 2005; 201(10):1615–1625.
Schaller E, Macfarlane AJ, Rupec RA et al. Inactivation of the F4/80 glycoprotein in the mouse germ line. Mol Cell Biol 2002; 22(22):8035–8043.
van den Berg TK, Kraal G. A function for the macrophage F4/80 molecule in tolerance induction. Trends Immunol 2005; 26(10):506–509.
Gordon S. The Legacy of cell fusion. Oxford; New York: Oxford University Press; 1994.
Ezekowitz RA, Austyn J, Stahl PD et al. Surface properties of bacillus Calmette-Guerin-activated mouse macrophages. Reduced expression of mannose-specific endocytosis, Fc receptors and antigen F4/80 accompanies induction of Ia. J Exp Med 1981; 154(1):60–76.
Hirsch S, Austyn JM, Gordon S. Expression of the macrophage-specific antigen F4/80 during differentiation of mouse bone marrow cells in culture. J Exp Med 1981; 154(3):713–725.
McGarry MP, Stewart CC. Murine eosinophil granulocytes bind the murine macrophage-monocyte specific monoclonal antibody F4/80. J Leukoc Biol 1991; 50(5):471–478.
Hume DA, Robinson AP, MacPherson GG et al. The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80. Relationship between macrophages, Langerhans cells, reticular cells and dendritic cells in lymphoid and hematopoietic organs. J Exp Med 1983; 158(5):1522–1536.
McKnight AJ, Gordon S. EGF-TM7: anovel subfamily of seven-transmembrane-region leukocyte cell-surface molecules. Immunol Today 1996; 17(6):283–287.
McKnight AJ, Gordon S. The EGF-TM7 family: unusual structures at the leukocyte surface. J Leukoc Biol 1998; 63(3):271–280.
Lee SH, Starkey PM, Gordon S. Quantitative analysis of total macrophage content in adult mouse tissues. Immunochemical studies with monoclonal antibody F4/80. J Exp Med 1985; 161(3):475–489.
Gordon S, Lawson L, Rabinowitz S et al. Antigen markers of macrophage differentiation in murine tissues. Curr Top Microbiol Immunol 1992; 181:1–37.
Ezekowitz RA, Gordon S. Down-regulation of mannosyl receptor-mediated endocytosis and antigen F4/80 in bacillus Calmette-Guerin-activated mouse macrophages. Role of T-lymphocytes and lymphokines. J Exp Med 1982; 155(6):1623–1637.
Ezekowitz RA, Gordon S. Surface properties of activated macrophages: sensitized lymphocytes, specific antigen and lymphokines reduce expression of antigen F4/80 and FC and mannose/fucosyl receptors, but induce Ia. Adv Exp Med Biol 1982; 155:401–407.
Haidl ID, Jefferies WA. Themacrophage cell surface glycoprotein F4/80 is ahighly glycosylated proteoglycan. Eur J Immunol 1996; 26(5):1139–1146.
Stacey M, Lin HH, Gordon S et al. LNB-TM7, a group of seven-transmembrane proteins related to family-B G-protein-coupled receptors. Trends Biochem Sci 2000; 25(6):284–289.
Kwakkenbos MJ, Kop EN, Stacey M et al. The EGF-TM7 family: a postgenomic view. Immunogenetics 2004; 55(10):655–666.
Baud V, Chissoe SL, Viegas-Pequignot E et al. EMR1, an unusual member in the family of hormone receptors with seven transmembrane segments. Genomics 1995; 26(2):334–344.
Hamann J, Koning N, Pouwels W et al. EMR1, the human homolog of F4/80, is an eosinophil-specific receptor. Eur J Immunol 2007; 37(10):2797–2802.
Yona S, Lin HH, Siu WO et al. Adhesion-GPCRs: emerging roles for novel receptors. Trends Biochem Sci 2008; 33(10):491–500.
McKnight AJ, Macfarlane AJ, Seldin MF et al. Chromosome mapping of the Emrl gene. Mamm Genome 1997; 8(12):946.
Kwakkenbos MJ, Matmati M, Madsen O et al. An unusual mode of concerted evolution of the EGF-TM7 receptor chimera EMR2. FASEB J 2006; 20(14):2582–2584.
Stacey M, Chang GW, Sanos SL et al. EMR4, a novel epidermal growth factor (EGF)-TM7 molecule up-regulated in activated mouse macrophages, binds to a putative cellular ligand on B lymphoma cell line A20. J Biol Chem 2002; 277(32):29283–29293.
O’Reilly D, Addley M, Quinn C et al. Functional analysis of the murine Emrl promoter identifies a novel purine-rich regulatory motif required for high-level gene expression in macrophages. Genomics 2004; 84(6):1030–1040.
Moriguchi T, Hamada M, Morito N et al. MafB is essential for renal development and F4/80 expression in macrophages. Mol Cell Biol 2006; 26(15):5715–5727.
Nakamura M, Hamada M, Hasegawa K et al. c-Maf is essential for the F4/80 expression in macrophages in vivo. Gene 2009; 445(1-2):66–72.
Warschkau H, Kiderlen AF. A monoclonal antibody directed against the murine macrophage surface molecule F4/80 modulates natural immune response to Listeria monocytogenes. J Immunol 1999; 163(6):3409–3416.
Stein-Streilein J. Immune regulation and the eye. Trends Immunol 2008; 29(11):548–554.
Stein-Streilein J, Taylor AW. An eye’s view of T regulatory cells. J Leukoc Biol 2007; 81(3):593–598.
Niederkorn JY. See no evil, hear no evil, do no evil: the lessons of immune privilege. Nat Immunol 2006; 7(4):354–359.
Faunce DE, Stein-Streilein J. NKT cell-derived RANTES recruits APCs and CD8+ T-cells to the spleen during the generation of regulatory T-cells in tolerance. J Immunol 2002; 169(1):31–38.
Hara Y, Caspi RR, Wiggert B et al. Analysis of an in vitro-generated signal that induces systemic immune deviation similar to that elicited by antigen injected into the anterior chamber of the eye. J Immunol 1992; 149(5):1531–1538.
Wilbanks GA, Mammolenti M, Streilein JW. Studies on the induction of anterior chamber-associated immune deviation (ACAID). II. Eye-derived cells participate in generating blood-borne signals that induce ACAID. J Immunol 1991; 146(9):3018–3024.
Wilbanks GA, Streilein JW. Studies on the induction of anterior chamber-associated immune deviation (ACAID). 1. Evidence that an antigen-specific, ACAID-inducing, cell-associated signal exists in the peripheral blood. J Immunol 1991; 146(8):2610–2617.
Lin HH, Chang GW, Huang YS et al. Multivalent protein probes for the identification and characterization of cognate cellular ligands for myeloid cell surface receptors. Methods Mol Biol 2009; 531:89–101.
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Lin, HH., Stacey, M., Stein-Streilein, J., Gordon, S. (2010). F4/80: The Macrophage-Specific Adhesion-GPCR and its Role in Immunoregulation. In: Yona, S., Stacey, M. (eds) Adhesion-GPCRs. Advances in Experimental Medicine and Biology, vol 706. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7913-1_13
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DOI: https://doi.org/10.1007/978-1-4419-7913-1_13
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