Open AccessSurface charge distribution is a determinant of antigen deposition in the renal glomerulus: studies employing ‘charge‐hybrid’ molecules
Author(s) -
BATSFORD S. R.,
MIHATSCH M. J.,
RAWIEL M.,
SCHMIEDEKE T. M.,
VOGT A.
Publication year - 1991
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1991.tb02955.x
Subject(s) - renal glomerulus , human serum albumin , chemistry , biophysics , molecule , lysine , immune system , lysozyme , glomerulus , immune complex , immunofluorescence , antibody , biochemistry , glomerulonephritis , biology , immunology , kidney , amino acid , endocrinology , organic chemistry
SUMMARY The deposition of antigens and immune complexes (IC) in the renal glomerulus is charge‐dependent. The demonstration that molecules of net anionic charge, but with discrete positively charged regions, exhibit affinity for the glomerular basement membrane (GBM) extends this concept. Charge hybrid (polar) molecules were constructed by covalently coupling small polycations (lysozyme or linear poly‐ l ‐lysinc chains with a mean of 17 and 20 residues) to larger polyanions (ovalbumin or human scrum albumin (HSA)). Although the products were of overall net anionic charge they still bound to glomerular structures. Immunofluorescence studies performed after i.v. injection of the samples into rats revealed that HSA:poly‐ l ‐lysine had the highest affinity. Radioisotopic measurements showed uptake of HSA: poly‐ l ‐lysinc to be a function of the number of lysinc residues; binding of HSA: poly‐ l ‐lysine 20 was 2.5 times higher than HSA:poly‐ l ‐lysine 17 ( P <0.01). Prior injection of a small competing polycation (polyethyleneimine 1200) reduced uptake of HSA:poly‐ l ‐lysine by 75%, indicating the charge‐based nature of the interaction. HSA:poly‐ l ‐lysine 20 alone was effectively eliminated from the glomeruli within 72 h. Administration of HSA:poly‐ l ‐lysine followed by anti‐HSA antibody induced immune complex formation in the capillary wall giving rise to a granular immunofluoresccnce pattern and discrete subendothelial and subepithelial deposits. Molecules with polar structure do occur naturally and may contribute to immune complex formation in glomerulonephritis.