Glomerular injury induced by cationic 70-kD staphylococcal protein; specific immune response is not involved in early phase in rats.
A highly cationic staphylococal protein (designated p70, MW 70 kD, pI > 10) belongs to the groups of bacterial proteins that can bind immunoglobulin without specific antigen-antibody recognition; heparin inhibition tests indicated a charge interaction. This study evaluated the nephritogenicity of p70, which has affinity for the glomerular basement membrane (GBM), and the influence of various mediator systems on the induction of glomerulonephritis by p70. The left kidneys of intact rats, rats given cobra venom factor (complement-depleted), or rats given anti-adhesion molecules (ICAM-1 and LFA-1a) were perfused with p70. Proteinuria started within 24 h and persisted at day 5. Intraglomerular infiltration of cells was seen as early as 15 min, peaking at day 1. Deposits of rat IgG and C3 were seen in a subendothelial location 15 min after p70 perfusion in the left kidney and were found in a predominantly subepithelial location from 1 day onwards. Complement depletion and blockade of adhesion molecules suppressed proteinuria from day 2 onwards; these manipulations also prevented the recruitment of infiltrating cells and partially hindered the transfer of IgG across the GBM and the accumulation of IgG in the subepithelial region. In the non-perfused right kidneys, deposits of IgG and C3 were comparable to those in the left kidneys, suggesting that p70-IgG complexes formed in the circulation may also contribute to the deposits in the GBM. Heparin inhibition tests indicated an electrostatic interaction between p70 and immunoglobulin. Complement and inflammatory mediator systems (granulocytes, monocytes/macrophages, and/or lymphocytes) were required to provoke glomerular injury. p70 might play a role in acute glomerulonephritis following Staphylococcus aureus infection.
Fujigaki
Y
Y
Abteilung Immunologie, Institut für Medizinische Mikrobiologie und Hygiene, Freiburg, Germany.
Yousif
Y
Y
Morioka
T
T
Batsford
S
S
Vogt
A
A
Hishida
A
A
Miyasaka
M
M
D000818:Animals; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism / Q000633:toxicity; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D001485:Basement Membrane / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D003176:Complement C3 / Q000032:analysis; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D006417:Hematuria / Q000276:immunology; D006493:Heparin / Q000494:pharmacology; D007074:Immunoglobulin G / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D016253:Microscopy, Immunoelectron; D011507:Proteinuria / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013211:Staphylococcus aureus / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D003176:Complement C3; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; C113110:cationic staphylococcal protein, 70-kDa; D006493:Heparin