Glomerular localization of nephritogenic protein complexes on a nonimmunologic basis.
BACKGROUND
In a preliminary study, we have found that a group of charge-distinct protein molecules can react with each other to form protein complexes in vitro. The present study was conducted to determine the nephritogenic effect and the mode of action of these proteins in vivo.


METHODS
To demonstrate the precipitating interactions, a phosphorylcholine (PC)-conjugated, cationized bovine serum albumin (BSA(+)-PC) was applied to react with dinitrophenyl (DNP)-protein conjugates by double diffusion test. The types of forces involved in binding actions were determined. The experimental groups of CDF1 mice were injected simultaneously with BSA(+)-PC and individual DNP-protein conjugates through the tail vein. Both clearance kinetics and renal tissue studies were performed.


RESULTS
BSA(+)-PC was able to form precipitin lines with respective DNP-protein conjugates in the agarose gel without any antigen-antibody interactions. These precipitating reactions were partially prevented by the presence of either NaCl, urea, or trifluoroacetate, suggesting that electrostatic force, hydrogen bond, and/or hydrophobic force are involved in the precipitation of these modified protein molecules. The clearance kinetics of BSA(+)-PC/BSA-DNP, and BSA(+)-PC/DNP-apoferritin showed a significant acceleration of the rapid phase of elimination. All of the experimental mice had hematuria and systemic thrombotic microangiopathic changes 1 hour later. By immunofluorescence, both the BSA(+)-PC and the DNP-protein conjugate injected were present in the renal glomerular tufts of experimental groups, although these protein molecules failed to deposit in the glomerulus when injected alone. Concomitant fibrinogen deposition was noted in almost all of the glomeruli affected. Moreover, 10 to 50% of the glomeruli examined 4 hours after injection had deposition of the third component of complement (C3).


CONCLUSIONS
These data strongly support a hypothesis that nondeposited nephritogenic protein molecules in a fashion of heterogeneous complexes can localize in the glomerulus, thereby initiating renal injury, with the lack of antibody involvement.
Chen
A
A
Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
Chou
W Y
WY
Ding
S L
SL
Shaio
M F
MF
D000818:Animals; D003165:Complement System Proteins / Q000378:metabolism; D004140:Dinitrophenols / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006241:Haptens / Q000378:metabolism*; D006417:Hematuria / Q000139:chemically induced; D007457:Iodine Radioisotopes; D007678:Kidney Glomerulus / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051379:Mice; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000378:metabolism* / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism; D013927:Thrombosis / Q000139:chemically induced / Q000473:pathology
D004140:Dinitrophenols; D006241:Haptens; D007457:Iodine Radioisotopes; C034638:dinitrophenyl-bovine serum albumin; C076110:phosphorylcholine-bovine serum albumin; D010767:Phosphorylcholine; D012710:Serum Albumin, Bovine; D003165:Complement System Proteins