INACTIVATION OF CELL-SURFACE RECEPTORS BY PHEOPHORBIDE-A, A GREEN PIGMENT ISOLATED FROM PSYCHOTRIA-ACUMINATA

The inhibition of cytokine and monoclonal antibody binding to cell sur faces caused by an extract of Psychotria acuminata, a medicinal plant used in the traditional medicine of the people of Belize (Central Amer ica), was attributed to the presence of pheophorbide a and pyropheopho rbide a. Since the binding of tumor necrosis factor-alpha, interleukin -8, complement factor 5a as well as epidermal growth factor to target cells was dramatically reduced, the inhibition was not receptor or cyt okine specific. In addition, the respective binding of radiolabeled mo noclonal antibodies CL203 and R15.7 to the cell surface antigens intra cellular cell adhesion molecule-1 and lymphocyte function-associated a ntigen-1 beta-chain was decreased by pretreatment of cells with pheoph orbide a as well. In all cases, the inhibition by pheophorbides was de pendent on the simultaneous presence of light, indicating causative in volvement of a photodynamic process. These observations are not unique to pheophorbides and can be extended to porphyrins as well as to othe r photodynamic agents. Cytotoxicity resulting from photodynamic therap y (PDT) has been documented by many studies. Our investigations sugges t that the inactivation of cell surface receptors contributes not only to the antitumor effect of PDT but also to the systemic immunosuppres sion, a serious side effect of PDT.