In vitro and in vivo regulation by macrophage migration inhibitory factor (MIF) of expression of MHC-II, costimulatory, adhesion, receptor, and cytokine molecules.
The secretion of macrophage migration inhibitory factor (MIF) is enhanced by inflammatory and other stimuli. MIF regulates innate and adaptive immune responses, but the mechanisms of this regulation are poorly understood. Our hypothesis was that MIF generated by these stimuli regulates these responses by modulating key molecular expression. This hypothesis was tested by adding greater than constitutive concentrations of recombinant MIF to cultures of various cell types and flow cytometric assay. MIF modulated surface expression of MHC-II, B7-2, CD40, CD40 ligand, ICAM-1 and Fcgamma, CR1/CR2, and IL-10 receptors and intracellular expression of IL-10, TNFalpha, and p40 (IL-12). MIF increased expression of B7-1 by B cells and CD40 L by T cells in spleens from Schistosoma mansoni-infected mice. Footpad injection of MIF reduced expression of MHC-II and CD40 by B cells in draining lymph nodes. Footpad injection of Mab to MIF reduced expression of B7-2 and CR1/CR2 by B cells and B7-2 by macrophages in these nodes. These data support our hypothesis.
Stavitsky
Abram B
AB
Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH 44120, USA. abs7@po.cwru.edu
Xianli
Jia
J
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand / Q000096:biosynthesis; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D051381:Rats; D011951:Receptors, Complement / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation
D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; C497966:Cd86 protein, rat; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand