Complement activation and inhibition: a delicate balance.
Complement is part of the innate immune defence and not only recognizes microbes but also unwanted host molecules to enhance phagocytosis and clearance. This process of opsonisation must be tightly regulated to prevent immunopathology. Endogenous ligands such as dying cells, extracellular matrix proteins, pentraxins, amyloid deposits, prions and DNA, all bind the complement activator C1q, but also interact with complement inhibitors C4b-binding protein and factor H. This contrasts to the interaction between C1q and immune complexes, in which case no inhibitors bind, resulting in full complement activation. Disturbances to the complement regulation on endogenous ligands can lead to diseases such as age-related macular degeneration, neurological and rheumatic disorders. A thorough understanding of these processes might be crucial to developing new therapeutic strategies.
Sjöberg
A P
AP
University of Copenhagen, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, DK-2200, Copenhagen, Denmark.
Trouw
L A
LA
Blom
A M
AM
D000544:Alzheimer Disease / Q000209:etiology / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000276:immunology; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology; D003167:Complement Activation / Q000276:immunology*; D050716:Complement C4b-Binding Protein; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D060588:LIM Domain Proteins; D008024:Ligands; D008268:Macular Degeneration / Q000209:etiology / Q000276:immunology; D009124:Muscle Proteins / Q000276:immunology / Q000378:metabolism; D017096:Prion Diseases / Q000209:etiology / Q000276:immunology; D011328:Prions / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding
D016229:Amyloid beta-Peptides; C055609:C4BPA protein, human; D050716:Complement C4b-Binding Protein; C101149:FHL1 protein, human; D006649:Histocompatibility Antigens; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008024:Ligands; D009124:Muscle Proteins; D011328:Prions; D003165:Complement System Proteins