T cell proliferative responses to malondialdehyde-acetaldehyde haptenated protein are scavenger receptor mediated.
Malondialdehyde-acetaldehyde (MAA) haptenated proteins have been described in disease processes related to prolonged oxidative stress (via malondialdehyde production), such as alcohol liver disease (ALD), non-alcoholic non-steatohepatitis (NASH) and atherosclerosis. Experimentally, high titer IgG1 antibody responses are seen after immunization without adjuvant; however, T cell proliferative responses and the role of scavenger receptors in this immunogenicity has not previously been described. In this study, T cell proliferative responses to the carrier protein, but not the MAA hapten itself, were identified in vitro. Moreover, these T proliferative responses were inhibited when MAA-hen egg lysozyme (HEL) was co-immunized with excess scavenger receptor ligand polyG (poly-guanylic acid), implicating the role of (a) scavenger receptor(s) in initiating the T helper cell response. Activated B cells were unable to process and present MAA-HEL preferentially to T cells, while thioglycollate-elicited (but not Con A-elicited) macrophages and dendritic cells (DC) did so with approximately 32-fold less MAA-HEL than native antigen necessary to initiate equal proliferative responses. While this preferential processing and presentation may be related to several factors, preferential binding of MAA haptenated proteins mediated by scavenger receptors may be one mechanism. IL-4 was absent from the supernatants of T proliferative assays despite a strong IgG1 response in vivo, although the TH2 cytokines IL-6 and IL-10 were expressed. Since the modification of proteins by the MAA have previously been shown to occur after ethanol consumption in vivo, the ability of MAA haptens to experimentally enhance immune responses, specifically humoral and T cell responses, may represent mechanisms by which autoimmune phenomena found in ALD occur.
Willis
Monte S
MS
Veterans Affairs Alcohol Research Center, Omaha Veterans Affairs Medical Center, 4101 Woolworth Ave., Omaha, NE 68105. montewillis@juno.com
Thiele
Geoffrey M
GM
Tuma
Dean J
DJ
Klassen
Lynell W
LW
D000079:Acetaldehyde / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006241:Haptens / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008315:Malondialdehyde / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009113:Muramidase / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D016207:Cytokines; D006241:Haptens; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D008315:Malondialdehyde; C421864:hen egg lysozyme; D009113:Muramidase; D000079:Acetaldehyde