Identification of macrophage cell-surface binding sites for cationized bovine serum albumin.
Autoimmune diseases are characterized by the presence of autoantibodies often restricted to host proteins exhibiting charge rich domains. Charged polypeptides elicit strong immune responses, and cationized bovine serum albumin and other cationic proteins are significantly more immunogenic than their less charged counterparts. These phenomena may involve enhanced protein uptake by macrophages, resulting in greater processing and presentation of antigenic peptide-MHC complexes to T-cells. We compared macrophage cell-surface binding and uptake of native and cationized bovine serum albumin. Specific binding of [125I]cationized bovine serum albumin to THP-1 macrophages in vitro was 11-16 fold greater than for native albumin. Half-maximal inhibition of [125I]cationized albumin binding was observed at 10-7M ligand. The specificity of [125I]cationized bovine serum albumin binding and uptake was further studied in terms of competitive inhibition of proteolysis by proteins of varying charge content. Cationized bovine serum albumin, but not native albumin, inhibited proteolysis of [125I]cBSA. Calf thymus histones also inhibited cBSA degradation. High concentration of myelin basic protein was moderately effective at blocking cBSA degradation, while myoglobin and beta lactalbumin showed no inhibition. These results indicate that specific cell-surface binding sites which occur on macrophages may mediate selective uptake of certain proteins with highly charged domains including some autoantigens.
Dohlman
J G
JG
Department of Medicine, University of Alabama Medical Center, Birmingham 35294.
Pillion
D J
DJ
Rokeach
L A
LA
Ramprasad
M P
MP
D001667:Binding, Competitive; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D004563:Electrochemistry; D010450:Endopeptidases / Q000378:metabolism; D005293:Ferritins / Q000737:chemistry / Q000494:pharmacology; D006657:Histones / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007526:Isoelectric Point; D007938:Leukemia; D008264:Macrophages / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000737:chemistry / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002412:Cations; D006657:Histones; D004676:Myelin Basic Protein; D012710:Serum Albumin, Bovine; D005293:Ferritins; D010450:Endopeptidases