Yoshimasa Nakano

A Complement Inhibitor Produced by Stachybotrys complementi, nov. sp. K-76, a New Species of Fungi Imperfecti

A complement inhibitor, K‐76, was isolated and purified from the culture supernatant of a fungus, Stachybotrys complementi, nov. sp. K‐76, isolated from soil of Ishigaki Island, Okinawa. K‐76 is a sesquiterpene compound and it can be oxidized to a monocarboxylic derivative (K‐76 COOH), the sodium salt of which is very soluble and much less toxic than K‐76. K‐76 and K‐76 COOH both inhibited complement activation by either the classical or alternative pathway. They inhibited generation of the factor chemotactic to human polymorphonuclear leukocytes from human serum by aggregated immunoglobulin. When sensitized erythrocytes were treated with complement in the presence of K‐76 COOH, the resulting unlysed cells were found to be in the state of EAC1, 4b, 2a, 3b. Thus K‐76 COOH is considered to block mainly the C5 intermediate step. K‐76 COOH did not inhibit any proteases or esterases tested, except when tested at high concentration.

Structure of K-76, a complement inhibitor produced by Stachybotrys complementi nov. Sp. K-76

The structure of ‘K-76’(1), a complement inhibitor containing a spirobenzofuran unit, obtained from Stachybotrys complementi nov. sp. K-76, is reported.

New rat model induced by anti‐glomerular basement membrane antibody shows severe glomerular adhesion in early stage and quickly progresses to end‐stage renal failure

The aim of the present study was to introduce a new anti‐glomerular basement membrane nephritis model in which plasma creatinine levels dramatically increased only 4 weeks after a single administration of rabbit antirat glomerular basement membrane antibody in Sprague–Dawley rats. According to renal morphology, glomerular lesions characterized by mesangial expansion and adhesion of the glomerular tuft to Bowmans capsule were observed in the early stage at day 7 after disease induction; adhesion was detected in approximately 90% of glomeruli 14 days after antibody injection. After 21 days the rats exhibited pronounced glomerulosclerosis/hyalinosis and severe tubulointerstitial lesions characterized by interstitial fibrosis. Urinary podocytes excreted in nephritis rats were studied and it was found that urinary podocyte loss might be closely related to progression of renal injury. Because this new model simply and reproducibly demonstrates development of end‐stage renal disease, it will be beneficial for elucidating mechanisms by which chronic renal injury irreversibly progresses, as well as for developing therapeutic agents for chronic renal failure.