title: Inhibition of the high affinity Fc receptor (Fc gamma RI) on human monocytes by porphyrin photosensitization is highly specific and mediated by the generation of superoxide radicals.
abstract: p72 high affinity receptors (Fc gamma RI) for the Fc portion of IgG molecules on human peripheral blood monocytes mediate a variety of beneficial functions, but also have deleterious effects in certain clinical situations. In the present study, the photosensitizing porphyrins hematoporphyrin derivative and dihematoporphyrin ether (DHE), which are known to preferentially affect the cell membrane, were found to significantly inhibit binding of mouse IgG2a antibodies to the ligand binding site of Fc gamma RI on human peripheral blood monocytes and the U937 human monocytic cell line. Fc gamma RI receptors could be identified with a monoclonal antibody which recognizes an epitope distinct from the ligand binding site, indicating that photosensitization induced a structural alteration rather than loss of the receptor molecule from the cell surface. The effect of DHE and light appeared to be highly specific, since binding of monoclonal antibodies to other surface structures was not decreased. DHE plus light-induced modulation of Fc gamma RI was found to be mediated by superoxide anions, since addition of a mimic of superoxide dismutase restored both binding of mouse IgG2a to Fc gamma RI as well as human monocyte accessory cell function. These studies identify porphyrin photosensitization as a unique mechanism by which to selectively down-regulate Fc gamma RI-mediated functions.
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: J
authors.initials: J
authors.lastname: Krutmann
authors.forename: M
authors.initials: M
authors.lastname: Athar
authors.forename: D B
authors.initials: DB
authors.lastname: Mendel
authors.forename: I U
authors.initials: IU
authors.lastname: Khan
authors.forename: P M
authors.initials: PM
authors.lastname: Guyre
authors.forename: H
authors.initials: H
authors.lastname: Mukhtar
authors.forename: C A
authors.initials: CA
authors.lastname: Elmets
mesh_terms: D000911:Antibodies, Monoclonal; D002460:Cell Line; D017323:Dihematoporphyrin Ether; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005609:Free Radicals; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008027:Light; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011961:Receptors, Fc / Q000187:drug effects* / Q000276:immunology; D013481:Superoxides / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D005609:Free Radicals; D006415:Hematoporphyrins; D007074:Immunoglobulin G; D011838:Radiation-Sensitizing Agents; D011961:Receptors, Fc; D013481:Superoxides; D017324:Hematoporphyrin Derivative; D017323:Dihematoporphyrin Ether