Anionization of an antigen promotes glomerular binding and immune complex formation.
Bovine serum albumin (BSA, pI 4.9) was maleylated to yield highly anionic MBSA (pI 3.0). Maleylation of BSA lead to an expansion of molecular size of native BSA from an effective molecular radius (EMR) of 37 A to 57 A for MBSA as assessed by gel filtration chromatography. MBSA, but not BSA, bound to the peripheral capillary wall (PCW) and mesangium in vitro in frozen sections, and in vivo following i.v. injection (0.006 mg/g body wt), examined by immunofluorescence. When similarly injected rats or controls were given antibodies to either MBSA or BSA following injection of antigen, immune complexes were observed in glomeruli by immunofluorescence and EM only in MBSA injected rats. Deposits occurred in the mesangium and subendothelium in the PCW. In frozen sections, bound MBSA could be partially removed from tissue sections by high ionic strength buffer. Also, binding of MBSA was diminished by prior treatment of sections with synthetic polyanions. Maleylated bovine gamma-globulin and succinylated BSA showed identical binding patterns as described for MBSA, indicating that binding was not unique to the modified BSA molecule nor to the form of anionization. These results indicate that charge interactions between circulating highly anionic macromolecules and cationic domains within glomerular structures are responsible, in part, for MBSA binding and subsequent localization of immune complexes. Furthermore, it is inferred that the selective binding of MBSA to glomeruli and formation of immune complexes occurred by a mechanism not related to difference in size between MBSA and BSA. These findings are different from conventionally understood charge interactions in glomerular immune complex formation.
Barnes
J L
JL
Department of Pathology, University of Texas Health Science Center, San Antonio.
Reznicek
M J
MJ
Radnik
R A
RA
Venkatachalam
M A
MA
D000418:Albumins / Q000378:metabolism; D000818:Animals; D000838:Anions / Q000378:metabolism*; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001485:Basement Membrane / Q000378:metabolism; D001667:Binding, Competitive; D005455:Fluorescent Antibody Technique; D007473:Ion Channels / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D046911:Macromolecular Substances; D011817:Rabbits; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism
D000418:Albumins; D000838:Anions; D000936:Antigen-Antibody Complex; D007473:Ion Channels; D046911:Macromolecular Substances; C049877:maleylalbumin; D012710:Serum Albumin, Bovine