Scand. J. Immunol. 26, 381-386, 1987 Immunohistochemical Detection of the Membrane and Fluid-phase Terminal Complement Complexes C5b-9(m) and SC5b-9 Consequences for Interpretation and Terminology T. E. MOLLNES & M. HARBOE Institute of Immunology and Rheumatology, The National Hospital, Oslo, Norway Mollncs. T. E. & Harboe. M. Immunohistochemical Detection of the Membrane and Fluid- phase Terminal Complement Complexes C5h-9(m) and SC5b-9. Consequences for Interpreta- tion and Terminology. Sca/nt. J. Immunol. 26, 3S1-.186. 1987 Activation of the terminal pathway of complement on a membrane results in the generation of the membrane-damaging terminal C3b-9{m) complcmeni complex, whereas Ihc non-lytic water-solubk SC.'ib-9 complex is formed when complement is activated in the fluid phase. Both forms of the terminal complement complex (TCC) can be immunohistochemically detected. but not distinguished, by antibodies recognizing neoantigens in the complexes. By means of monoclonal antibodies against C9 neoantigens and against the S-protein. it was demonstrated that deposits of the TCC in tissue seetions may be either in the form of C5b-9(m) or SC5b-9. I'he consequences of this for the interpretation of the histochemieal data and the terminology of the two complexes are discussed. Tom Eirik Mottnes. Instimie of Immunology and Rheumalotogy. Fr. Qvamsgi. I, 0172 Oslo I. Norwav The terminal complement complex (TCC) exists in two analogous forms, depending on the site of activation (for reviews see Refs3. 22.24 and 2?). When activated on a membrane the five terminal components assemble into the C5b-9(m) com- plex, which penetrates the membrane due to its lipophilic properties, thereby creating a stable transmembrane pore with a central hydrophilic channel. These events may lead to tnembrane damage and eventually cell lysis, depending on the ability of the cell to repair the damage. In conirasL the TCC is water soluble and non-lytic if the components assemble as SC5b-9 in the fluid phase, due to the association of C5b-9 with the S-protein. Further, generation of C5b-9(m) is associated with release of inflammatory pro- ducts from the arachidonicacid pathway [14. IS) and with production of reactive oxygen metabolites [ 1 ]. whereas neither of these effects were observed with SC5b-9. Neoantigens present in the TCC but absent from the native components were first demonstrated in vitro [2. 21]. Several monoclo- nal antibodies specific for such neoantigens have been characterized 113.17. 23], but none of them can distinguish C5b-9(m) from SC5b-9. In vivo, TCC neoantigens have been demonstrated in fibrous plaques of human aorta [26, 30]. in the dermal-epidermal junction in systemic lupus erythematosus (SLE) [7[ and bulious pemphigoid [ID], in the dermal papillae in dermatitis herpetiformis [11], and in small vessels in dermatomyositis |20]. Several authors have reported TCC neoantigens in normal and diseased kidneys [6, 8. 13. 16, 27[. In severe diseased kidneys, glomerular, interstitial, and tubular/peritubular deposits of C9 neoantigens were found. Normal kidneys stained weakly in connective tisstie matrices and occasionally in vessels, which was interpreted as participation of complement in the normal cell turnover. Two review papers have discussed the pathogenic role of TCC. partly on the basis of demonstra- tion of neoantigens locally in the tissues [6, 9]. Some of the data are conflicting, particularly the relation between neoantigens and impairment of 381