TY - JOUR
T1 - Direct binding of C1q to apoptotic cells and cell blebs induces complement activation
AU - Nauta, Alma J.
AU - Trouw, Leendert A.
AU - Daha, Mohamed R.
AU - Tijsma, Odette
AU - Nieuwland, Rienk
AU - Schwaeble, Wilhelm J.
AU - Gingras, Alexandre R.
AU - Mantovani, Alberto
AU - Hack, Erik C.
AU - Roos, Anja
PY - 2002
Y1 - 2002
N2 - Deficiency of early components of the classical pathway of complement, particularly C1q, predisposes to the development of systemic lupus erythematosus. Several studies have suggested an association between the classical complement pathway and the clearance of apoptotic cells. Mice with a targeted deletion of the C1q gene develop a lupus-like renal disease, which is associated with the presence of multiple apoptotic bodies in the kidney. In the present study we demonstrate that highly purified C1q binds to apoptotic cells and isolated blebs derived from these apoptotic cells. Binding of C1q to apoptotic cells occurs via the globular heads of C1q and induces activation of the classical complement pathway, as shown by the deposition of C4 and C3 on the surface of these cells and on cell-derived blebs. In addition, for the first time, we demonstrate that surface-bound C1q is present on a subpopulation of microparticles isolated from human plasma. Taken together, these observations demonstrate that C1q binds directly to apoptotic cells and blebs derived therefrom and support a role for C1q, possibly in concert with C4 and C3, in the clearance of apoptotic cells and blebs by the phagocytic system
AB - Deficiency of early components of the classical pathway of complement, particularly C1q, predisposes to the development of systemic lupus erythematosus. Several studies have suggested an association between the classical complement pathway and the clearance of apoptotic cells. Mice with a targeted deletion of the C1q gene develop a lupus-like renal disease, which is associated with the presence of multiple apoptotic bodies in the kidney. In the present study we demonstrate that highly purified C1q binds to apoptotic cells and isolated blebs derived from these apoptotic cells. Binding of C1q to apoptotic cells occurs via the globular heads of C1q and induces activation of the classical complement pathway, as shown by the deposition of C4 and C3 on the surface of these cells and on cell-derived blebs. In addition, for the first time, we demonstrate that surface-bound C1q is present on a subpopulation of microparticles isolated from human plasma. Taken together, these observations demonstrate that C1q binds directly to apoptotic cells and blebs derived therefrom and support a role for C1q, possibly in concert with C4 and C3, in the clearance of apoptotic cells and blebs by the phagocytic system
U2 - https://doi.org/10.1002/1521-4141(200206)32:6<1726::AID-IMMU1726>3.0.CO;2-R
DO - https://doi.org/10.1002/1521-4141(200206)32:6<1726::AID-IMMU1726>3.0.CO;2-R
M3 - Article
C2 - 12115656
SN - 0014-2980
VL - 32
SP - 1726
EP - 1736
JO - European journal of immunology
JF - European journal of immunology
IS - 6
ER -