MONOCLONAL-ANTIBODIES AGAINST THE HUMAN MANNOSE RECEPTOR THAT INHIBITTHE BINDING OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR

To study the role of the mannose receptor in cellular uptake and degra dation of tissue-type plasminogen activator (t-PA), a set of five mono clonal antibodies (Moab) was generated against the mannose receptor is olated from human placental tissue. All Moab specifically recognised t he 175 kDa mannose receptor in a crude placenta extract, as shown in W estern blot analysis. By use of immunohistochemistry, we showed that i n human placenta only the Hofbauer cells (fetal macrophages) express t he mannose receptor. Epitope competition experiments indicated that th e Moab bound to at least two different epitopes on the receptor molecu le. Moab 14-3, 14-5, and 15-2, which are directed against one of these epitopes, strongly inhibited the interaction between the purified man nose receptor and t-PA. These Moab also inhibited mannose receptor-med iated degradation of t-PA by cultured human macrophages. The low densi ty lipoprotein receptor-related protein (LRP) mediated t-PA degradatio n was not affected by the Moab. It is concluded that the Moab are usef ul for studying the expression of the human mannose receptor in Wester n blot and in immunohistochemistry, and for studying the interactions between the human mannose receptor and the mannose-containing ligand t -PA.