Histones have high affinity for the glomerular basement membrane. Relevance for immune complex formation in lupus nephritis

Journal Article · Thu Jun 01 04:00:00 EDT 1989 · J. Exp. Med.; (United States)

DOI:https://doi.org/10.1084/jem.169.6.1879· OSTI ID:5879150

Schmiedeke, T M; Stoeckl, F W.W.; Weber, R; Sugisaki, Y; Batsford, S R; Vogt, A

An effort has been made to integrate insights on charge-based interactions in immune complex glomerulonephritis with nuclear antigen involvement in lupus nephritis. Attention was focussed on the histones, a group of highly cationic nuclear constituents, which could be expected to bind to fixed anionic sites present in the glomerular basement membrane (GBM). We demonstrated that all histone subfractions, prepared according to Johns, have a high affinity for GBM and the basement membrane of peritubular capillaries. Tissue uptake of /sup 125/I-labeled histones was measured by injecting 200 micrograms of each fraction into the left kidney via the aorta and measuring organ uptake after 15 min. In glomeruli isolated from the left kidneys, the following quantities of histones were found: f1, 13 micrograms; f2a (f2al + f2a2), 17 micrograms; f2b, 17 micrograms; and f3, 32 micrograms. Kinetic studies of glomerular binding showed that f1 disappeared much more rapidly than f2a. The high affinity of histones (pI between 10.5 and 11.0; mol wt 10,000-22,000) for the GBM correlates well with their ability to form aggregates (mol wt greater than 100,000) for comparison lysozyme (pI 11, mol wt 14,000), which does not aggregate spontaneously bound poorly (0.4 micrograms in isolated glomeruli). The quantity of histones and lysozyme found in the isolated glomeruli paralleled their in vitro affinity for a Heparin-Sepharose column (gradient elution studies). This gel matrix contains the sulfated, highly anionic polysaccharide heparin, which is similar to the negatively charged heparan sulfate present in the GBM. Lysozyme eluted with 0.15 M NaCl, f1 with 1 M NaCl, and f2a, f2b, and f3 could not be fully desorbed even with 2 M NaCl; 6 M guanidine-HCl was necessary.

• Research Organization: Institute of Medical Microbiology, Freiburg (Germany, F.R.)
• OSTI ID: 5879150
• Journal Information: J. Exp. Med.; (United States), Journal Name: J. Exp. Med.; (United States) Vol. 169:6; ISSN JEMEA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
AFFINITY
AMINES
ANIMALS
ANTICOAGULANTS
ANTIGEN-ANTIBODY REACTIONS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CARBOHYDRATES
CELL CONSTITUENTS
CELL MEMBRANES
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HEMATOLOGIC AGENTS
HEPARIN
HISTONES
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
INTRAVENOUS INJECTION
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
MUCOPOLYSACCHARIDES
NUCLEI
NUCLEIC ACIDS
NUCLEOPROTEINS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
POLYSACCHARIDES
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SACCHARIDES
SEPARATION PROCESSES
SPECIFICITY
TRACER TECHNIQUES
UROGENITAL SYSTEM DISEASES
VERTEBRATES