Complement components of the innate immune system in health and disease inthe CNS

The innate immune system and notably the complement (C) system play importa nt roles in host defense to recognise and kill deleterious invaders or toxi c entities, but activation at inappropriate sites or to an excessive degree can cause severe tissue damage. C has been implicated as a factor in the e xacerbation and propagation of tissue injury in numerous diseases including neurodegenerative disorders. In this article, we review the evidence indic ating that brain cells can synthesise a full lytic C system and also expres s specific C inhibitors (to protect from C activation and C lysis) and C re ceptors (involved in cell activation, chemotaxis and phagocytosis). We also summarise the mechanisms involved in the antibody-independent activation o f the classical pathway of C in Alzheimer's disease, Huntington's disease a nd Pick's disease. Although the primary role of C activation on a target ce ll is to induce cell lysis (particularly of neurons), we present evidence i ndicating that C (C3a, C5a, sublytic level of C5b-9) may also be involved i n pro- as well as anti-inflammatory activities. Moreover, we discuss eviden ce suggesting that local C activation may contribute to tissue remodelling activities during repair in the CNS. (C) 2000 Elsevier Science B.V. All rig hts reserved.