Complement activation and inhibition: a delicate balance

TY - JOUR

T1 - Complement activation and inhibition: a delicate balance

AU - Sjöberg, A P

AU - Trouw, L A

AU - Blom, A M

N1 - Keywords: Alzheimer Disease; Amyloid beta-Protein; Animals; Arthritis, Rheumatoid; Complement Activation; Complement System Proteins; Histocompatibility Antigens; Humans; Immunity, Innate; Intracellular Signaling Peptides and Proteins; Ligands; Macular Degeneration; Muscle Proteins; Prion Diseases; Prions; Protein Binding

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1016/j.it.2008.11.003

DO - 10.1016/j.it.2008.11.003

M3 - Journal article

C2 - 19144569

SN - 1471-4906

VL - 30

SP - 83

EP - 90

JO - Trends in Immunology

JF - Trends in Immunology

IS - 2

ER -