Macrophages express membrane bound form of APRIL that can generate immunomodulatory signals.
Members of the tumour necrosis factor superfamily play an essential role in inducing various biological responses including proliferation, differentiation, survival and cell death. A proliferation-inducing ligand (APRIL), first identified as a stimulant of tumour proliferation, is now known as a regulator of B-cell-mediated immune responses through the modulation of B-cell survival and activation. However, the role of APRIL in macrophage function has not been explored. High level expression of APRIL was detected on the surface of cells of the monocytic lineage including the human macrophage-like cell line, THP-1. To identify the role of APRIL in macrophage functions, THP-1 cells were stimulated with either its counterpart (TACI : Fc fusion protein) or a monoclonal antibody that is specific to APRIL. Stimulation of APRIL resulted in the expression of pro-inflammatory mediators such as interleukin-8 and matrix metalloproteinase-9 through the activation of mitogen-activated protein kinase and nuclear factor-κB. In contrast, stimulation of APRIL had an inhibitory effect on processes that require cytoskeletal movement such as phagocytosis of opsonized zymosan and chemotaxis through an inhibition of phosphatidylinositol 3-kinase activity. These observations demonstrate that macrophages express a membrane-bound form of APRIL which, upon stimulation, modulates the activities of macrophages through stimulation or inhibition of processes associated with inflammation.
School of Life Sciences and Biotechnology, Kyungpook National University, Daegu, Korea.
Sang-Min
SM
Lee
Sung-Tak
ST
Jeon
Kyoungho
K
Suk
Won-Ha
WH
Lee
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002633:Chemotaxis / Q000276:immunology; D003599:Cytoskeleton / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation / Q000276:immunology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018836:Inflammation Mediators; D016209:Interleukin-8; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D019869:Phosphatidylinositol 3-Kinases; D020780:Matrix Metalloproteinase 9; C524618:TACI receptor-IgG Fc fragment fusion protein