Distinct and separable roles of the complement system in factor H-deficient bone marrow chimeric mice with immune complex disease.
Plasma complement factor H (Cfh) is a potent complement regulator, whereas Cfh on the surface of rodent platelets is responsible for immune complex processing. For dissection between the two, bone marrow chimeras between Cfh-deficient (Cfh(-/-)) and wild-type C57BL/6 mice were created. Platelet Cfh protein was tracked with the Cfh status of the bone marrow donor, indicating that platelet Cfh is of intrinsic origin. In an active model of immune complex disease, Cfh(-/-) mice that were reconstituted with wild-type bone marrow had levels of platelet-associated immune complexes comparable to those of wild-type mice and were protected against the excessive glomerular deposition of immune complexes seen in Cfh(-/-) mice, yet these mice still developed glomerular inflammation. In contrast, wild-type mice with Cfh(-/-) bone marrow had reduced platelet-associated immune complexes and extensive glomerular deposition of complement-activating immune complexes, but they did not develop glomerular pathology. The large quantities of glomerular C3 in wild-type mice with Cfh(-/-) bone marrow were in the form of iC3b and C3dg, whereas active C3b remained in Cfh(-/-) recipients of wild-type bone marrow. These data show that plasma Cfh limits complement activation in the circulation and other accessible sites such as the glomerulus, whereas platelet Cfh is responsible for immune complex processing.
Alexander
Jessy J
JJ
Section of Nephrology, The University of Chicago, AMB S-508, MC 5100, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.
Aneziokoro
O G B
OG
Chang
Anthony
A
Hack
Bradley K
BK
Markaryan
Adam
A
Jacob
Alexander
A
Luo
Roger
R
Thirman
Michael
M
Haas
Mark
M
Quigg
Richard J
RJ
D000818:Animals; D001792:Blood Platelets / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D002478:Cells, Cultured; D017242:Complement Factor H / Q000172:deficiency* / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D007105:Immune Complex Diseases / Q000276:immunology*; D007668:Kidney / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D017242:Complement Factor H; D003165:Complement System Proteins