Membrane complement regulatory proteins in autoimmune and inflammatory tissue injury.
The complement system plays a complex role in the pathogenesis of autoimmune diseases. It inhibits autoimmunity development by helping to maintain self-tolerance and/or by facilitating the disposal of immune complexes and apoptotic cell antigens. On the other hand, complement activation is thought to contribute significantly to end organ damage in antibody-mediated autoimmune and inflammatory conditions, although the relevant importance of complement and Fe receptor pathways in these processes has recently been debated. To avoid autologous complement-mediated tissue injury, host cells normally express a number of soluble and membrane-bound complement regulatory proteins. Recent studies with gene knockout mice have suggested that membrane-bound complement regulatory proteins may critically determine the sensitivity of host tissues to complement injury in autoimmune and inflammatory disorders. Evidence is also accumulating to support the hypothesis that membrane complement regulatory proteins may not only inhibit complement-mediated injury during the effector phase of autoimmunity but also influence the adaptive immune response through complement-dependent or -independent mechanisms. The latter mechanism is likely related to their potential as cell surface signaling molecules.
Song
Wen-Chao
WC
Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pa., USA. Song@spirit.gcrc.upenn.edu
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001327:Autoimmune Diseases / Q000209:etiology*; D018958:CD55 Antigens / Q000502:physiology*; D018957:CD59 Antigens / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000502:physiology*; D023421:Models, Animal; D017463:Receptors, Complement 3b / Q000502:physiology*
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D017463:Receptors, Complement 3b