Decay-accelerating factor expression in the rat kidney is restricted to the apical surface of podocytes.
BACKGROUND
Decay-accelerating factor (DAF) has inhibitory activity toward complement C3 and C5 convertases. DAF is present in human glomeruli and on cultured human glomerular visceral epithelial cells (GEC). We studied the distribution and function of rat DAF.


METHODS
Function-neutralizing antibodies (Abs) were raised against DAF. The distribution of DAF in vivo was determined by immunoelectron microscopy. Functional studies were performed in cultured GEC and following IV injection of anti-DAF Abs into rats.


RESULTS
DAF was present exclusively on the apical surfaces of GEC, and was not present on the basal surfaces of GEC, nor other glomerular or kidney cells. DAF was functionally active on cultured GEC, and served to limit complement activation in concert with CD59, an inhibitor of C5b-9 formation. Upon injection into normal rats, anti-DAF F(ab')2 Abs bound to GEC in vivo, yet there was no evidence for complement activation and animals did not develop abnormal albuminuria. Anti-megalin complement-activating IgG Abs were "planted" on GEC, which activated complement as evidenced by the presence of C3d on GEC. Attempts to inhibit DAF function with anti-DAF Abs did not affect the quantity of complement activation by these anti-megalin Abs, nor did it lead to development of abnormal albuminuria. In contrast, in the puromycin aminonucleoside model of GEC injury and proteinuria, anti-DAF Abs slowed the recovery from renal failure that occurs in this model.


CONCLUSIONS
In cultured rat GEC, DAF is an effective complement regulator. In vivo, DAF is present on GEC apical surfaces. Yet, it appears that DAF is not essential to prevent complement activation from occurring under normal circumstances and in those cases in which complement-activating Abs are present on the basal surfaces of GEC in vivo. However, in proteinuric conditions, DAF appears to be protective to GEC.
Bao
Lihua
L
Section of Nephrology, The University of Chicago, Chicago, Illinois 60637, USA. lbao@medicine.uchicago.edu
Spiller
O Brad
OB
St  John
Patricia L
PL
Haas
Mark
M
Hack
Bradley K
BK
Ren
Guohui
G
Cunningham
Patrick N
PN
Doshi
Mona
M
Abrahamson
Dale R
DR
Morgan
B Paul
BP
Quigg
Richard J
RJ
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018958:CD55 Antigens / Q000032:analysis* / Q000276:immunology; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D003167:Complement Activation; D004847:Epithelial Cells / Q000737:chemistry / Q000648:ultrastructure; D004912:Erythrocytes / Q000737:chemistry; D019084:Fluorescent Antibody Technique, Indirect; D005920:Glomerular Mesangium / Q000737:chemistry* / Q000166:cytology* / Q000276:immunology; D008297:Male; D016253:Microscopy, Immunoelectron; D009401:Nephrosis / Q000276:immunology / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D018958:CD55 Antigens