Activation of the lectin pathway in murine lupus nephritis.
In systemic lupus erythematosus (SLE), hypocomplementaemia and complement deposition have been described both in man and in experimental models. A major involvement of the classical pathway of complement activation has been demonstrated in this disease, however relatively little is known about the involvement of the lectin pathway. Therefore in the present study we have analyzed the activity of all three pathways of complement activation in murine models of SLE. In the mouse, MBL is expressed in two forms, namely MBL-A and MBL-C. In the present study young and old MRL-lpr and control MRL+/+ mice were compared for the levels of complement activity with specific attention for the lectin pathway. It was found that upon aging of both MRL-lpr and MRL+/+ mice, a marked decrease in the activity of the classical pathway (CP) occurs. Levels of alternative pathway (AP) and lectin pathway (LP) activity remain unchanged. Key-molecules of these pathways, C1q, C3, MBL-A and MBL-C were analyzed and were all found to be decreased in aged mice of both strains. The levels of MBL-A and MBL-C showed a high degree of correlation and decreased equally. In aged MRL-lpr mice in which autoimmunity is most pronounced, we observed high autoantibody titers and strong deposition of glomerular immune complexes in association with deposition of C1q, C3, MBL-A and MBL-C. In conclusion, these data suggest that in addition to the classical pathway and the alternative pathway also the lectin pathway of complement activation is involved in murine lupus nephritis.
Trouw
Leendert A
LA
Department of Nephrology, C3, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. leendert.trouw@klkiemi.mas.lu.se
Seelen
Marc A
MA
Duijs
Jacques M G J
JM
Wagner
Sven
S
Loos
Michael
M
Bajema
Ingeborg M
IM
van Kooten
Cees
C
Roos
Anja
A
Daha
Mohamed R
MR
D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D037102:Lectins / Q000378:metabolism*; D008181:Lupus Nephritis / Q000378:metabolism*; D051379:Mice; D019463:Mice, Inbred MRL lpr
D001323:Autoantibodies; D037102:Lectins