Effects of excess factor D on early- and late-phase activation of the complement cascade.
The present study was undertaken to examine the effects of excess factor D build-up in the body of end-stage renal disease (ESRD) patients upon the activation of the alternative pathway and the terminal pathway in the fluid phase. First, to clarify the effect of excess factor D on the alternative pathway, purified factor D from an ESRD patient was added to normal serum and the changes in concentrations of C3a-des-Arg and C5a-des-Arg were investigated. The results showed that once the serum factor D level reached a concentration corresponding to 15 micrograms/ml in the serum of the ESRD patient, the C3a-des-Arg and C5a-des-Arg levels had climbed to about 1.7-fold the concentration in normal serum. Next, in order to clarify the effect of excess factor D on the terminal pathway, purified factor D was added to normal serum, and the changes in C5b6 generation were examined. The results indicated that as the factor D level increased in the serum, the C5b6 level rose gradually also; and when the factor D concentration reached 15 micrograms/ml, the C5b6 generation had risen to approximately 1.5-fold the level in normal serum. The present results therefore suggest that factor D build-up in ESRD patients provides a uremic toxin that can cause abnormal activation of the whole complement cascade.
Kobayakawa
H
H
Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Miyata
T
T
Inagi
R
R
Shinzato
T
T
Maeda
K
K
D003166:Complement Activating Enzymes / Q000494:pharmacology*; D003167:Complement Activation; D015926:Complement C3a / Q000378:metabolism; D011416:Complement Factor D / Q000378:metabolism*; D003170:Complement Pathway, Alternative; D006801:Humans; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000276:immunology
C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; D003166:Complement Activating Enzymes; C493488:CFD protein, human; D011416:Complement Factor D