Pathogenicity of catalytic antibodies: catalytic activity of Bence Jones proteins from myeloma patients with renal impairment can elicit cytotoxic effects.
Some Bence Jones proteins (BJPs) can display catalytic activity. Although the catalytic activity of BJPs might be associated with the pathogenesis of disease, this relationship has not yet been established. We tested the effects of seven BJPs on LLC-PK1 cells to assess their pathogenicity. Two out of the seven BJPs showed cytotoxic activity, as assessed by microscopic analysis, the WST method and TUNEL staining. Moreover, the cytotoxic BJPs were excreted by patients who presented with renal impairment. The cytotoxic BJPs displayed 20- to 40-fold higher catalytic activities (kcat of 3.5-2.2 min(-1)) in hydrolyzing a chromogenic substrate compared to the other BJPs. By treating the cytotoxic BJPs with diisopropylfluorophosphate, they lost not only their catalytic activity, but also the cytotoxic effects. These results indicate a direct link between cytotoxicity and the catalytic activity of the BJPs. The catalytic activity of BJPs contributes to the pathogenesis, as well as to development, of symptoms of multiple myeloma. Inhibition of the catalytic activity of BJPs may form the basis of a novel treatment for multiple myeloma patients with renal dysfunction.
Matsuura
Kinji
K
Hanada Clinic and Laboratory, 3-13 Higashiasakayamacho, Sakai, Osaka 591-8008, Japan. knhanada@ares.eonet.ne.jp
Ohara
Kyoko
K
Munakata
Hiroshi
H
Hifumi
Emi
E
Uda
Taizo
T
D000818:Animals; D017151:Antibodies, Catalytic / Q000378:metabolism* / Q000633:toxicity; D001536:Bence Jones Protein / Q000276:immunology / Q000378:metabolism* / Q000633:toxicity; D002384:Catalysis; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D005459:Fluorides / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007674:Kidney Diseases / Q000652:urine; D007700:Kinetics; D018374:LLC-PK1 Cells; D008858:Microscopy, Phase-Contrast; D009101:Multiple Myeloma / Q000652:urine; D010710:Phosphates / Q000378:metabolism / Q000494:pharmacology; D013552:Swine
D017151:Antibodies, Catalytic; D010710:Phosphates; C012980:fluorophosphate; D001536:Bence Jones Protein; D005459:Fluorides