Iron Salts and Iron-Containing Porphyrins Block Presentation of Protein Antigens by Macrophages to MHC Class II-Restricted T Cells

Author： Carrasco-Marin E. Alvarez-Dominguez C. Lopez-Mato P. Martinez-Palencia R. Leyva-Cobian F.

Publisher： Academic Press

ISSN： 0008-8749

Source： Cellular Immunology, Vol.171, Iss.1, 1996-08, pp. : 173-185

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

In this report we present evidence indicating that red blood cells (RBC) and a soluble lysate derived from them, but neither RBC membranes nor several highly purified erythrocytic glycolipids, impaired antigen presentation. Hematoporphyrin and some defined hemoglobin degradation products (specifically iron-containing porphyrins) are the molecules responsible for antigen presentation inhibition in Mphi. Although these metalloporphyrins did not inhibit antigen presentation in B cells or dendritic cells (DC), iron salts impaired antigen presentation in all antigen presenting cells (APC) tested. These effects were time and dose-dependent and occurred at the level of intracellular antigen processing, mainly because: (i) The inhibition was nontoxic; (ii) it was reversible with time; (iii) neither antigen uptake and catabolism nor de novo synthesis of IA molecules were affected; and (iv) it did not inhibit peptide binding to IA molecules and recognition by T cells. Finally, iron salts and metalloporphyrins generated lipid peroxidation by-products in APC in a dose-dependent manner. Production of lipid peroxides was clearly correlated with antigen processing interference. It is suggested that some porphyrins and free iron could be responsible for peroxidation of key lipids involved in specific protein interactions in antigen processing. These results may help to explain, at least partly, the impaired cellular immunity observed in several disorders associated with enhanced erythrophagocytosis and/or iron overload.