The Effect of the Cleavage Peptide C3aDesArg of the Third Complement Component on the Accumulation of Leukocytes in Cerebrospinal Fluid (CSF) and on the Permeability of the Blood-CSF Barrier

Abstract

Complement is an important humoral effector system of the immune response (5, 8). It is a set of nine serum proteins which can be triggered by antigen-antibody complexes to initiate an exactly defined cascade of proteolytic and protein-binding reactions (Fig. 1), so-called complement activation (5, 8). This finally leads to phagocytosis and lysis of foreign cells. Apart from this main pathway an alternative pathway (Fig. 1) of complement activation by endotoxins is known (5, 8) The fact that its activation can also be triggered by plasmin and Hageman factor fragment (Fig. 1) links complement to other important humoral effector systems, the fibrinolytic, coagulation, and kallikreinkinin systems. During complement activation C3a arises as a cleavage peptide of the third complement component and is rapidly transformed into C3aDesArg by a serum carboxypeptidase (8). Like C3a, C3aDesArg increases vascular permeability and causes chemotaxis of leukocytes (1, 2, 4). These properties make both peptides potent mediators of inflammation. It had not yet been demonstrated that the experimental application of complement-derived polypeptides to the CSF caused an inflammatory response including the increase of cell counts and an increase of the permeability of the blood-CSF barrier. We studied this using the more stable polypeptide C3aDesArg.