title: Regulation of HLA-DR and invariant chain expression by human peripheral blood mononuclear cells with lead, interferon-gamma, or interleukin-4.
abstract: It has been reported that the expression of major histocompatibility complex (MHC) class II can be regulated by lead (Pb) in murine cells. In both human and mouse, the expression of MHC class II and invariant chain (Ii) can be regulated by cytokines, including interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). Herein we report that in humans, as with IL-4, Pb enhanced MHC class II antigen DR (HLA-DR) surface expression by monocytes and B cells; Ii surface expression by monocytes and B cells was not affected by Pb while it was enhanced by IL-4. IFN-gamma increased HLA-DR and Ii surface expression by monocytes but it decreased HLA-DR and Ii surface expression by B cells. Total cellular HLA-DR expression by peripheral blood mononuclear cells (PBMC) was increased by Pb, IFN-gamma, or IL-4. Total cellular Ii (p33 and p35) expression by PRMC was not affected by Pb or IFN-gamma while it was increased by IL-4. In PBMC, the steady-state mRNA levels of HLA-DR alpha and Ii were not affected by Pb; IFN-gamma increased HLA-DR alpha mRNA expression but not Ii; IL-4 increased both mRNA levels of HLA-DR alpha and Ii. Furthermore, Pb, IFN-gamma, or IL-4 significantly increased the total cellular level of HLA-DR:Ii complexes in PBMC while they had no effect on cell surface HLA-DR:Ii complex expression. Overall, these results suggest that, in vitro, Pb, IFN-gamma, and IL-4 differentially modulate HLA-DR and Ii expression by human PBMC.
authors.affiliation: Department of Pathology and Laboratory Medicine, Albany Medical College, New York 12208, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Guo
authors.forename: S P
authors.initials: SP
authors.lastname: Mudzinski
authors.forename: D A
authors.initials: DA
authors.lastname: Lawrence
mesh_terms: D000293:Adolescent; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis* / Q000187:drug effects; D004357:Drug Synergism; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D007854:Lead / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; C045084:invariant chain; D015847:Interleukin-4; D007854:Lead; C029891:lead chloride; D007371:Interferon-gamma