Efficacy of an immunotoxin to folate receptor beta in the intra-articular treatment of antigen-induced arthritis

نویسندگان

  • Taku Nagai
  • Akira Kyo
  • Kazuhisa Hasui
  • Sonshin Takao
  • Takami Matsuyama
چکیده

INTRODUCTION We previously demonstrated that synovial sublining macrophages express folate receptor beta (FRβ). The aim of this study was to evaluate the efficacy of intra-articular administration of a recombinant immunotoxin to FRβ for treating rat antigen-induced arthritis. METHODS A monoclonal antibody (mAb) to rat FRβ was produced by immunizing mice with B300-19 cells (murine pre-B cells) transfected with the rat FRβ gene. Recombinant immunotoxin was prepared by conjugating the Fv portion of the anti-rat FRβ mAb heavy chain with a truncated Pseudomonas exotoxin A and the Fv portion of the anti-rat FRβ mAb light chain. Antigen-induced arthritis was induced through intra-articular injection of methylated bovine serum albumin (mBSA) after two subcutaneous injections of mBSA and complete Freund's adjuvant. Immunotoxin was intra-articularly injected into the arthritis joint every other day for seven days after arthritis onset. Joint swelling was measured and histological scores of inflammation, synovial thickness, cartilage, and bone destruction were determined. Immunohistochemistry was performed to detect osteoclast and osteoclast precursor FRβ-expressing macrophages and cathepsin K-positive cells on day 21. RESULTS Intra-articular administration of the immunotoxin attenuated joint swelling (61% suppression; P < 0.01 compared to the control on day 21) and improved histological findings, particularly cartilage and bone destruction (scores of rats treated with control versus the immunotoxin: 2.2 versus 0.5; P < 0.01), by reducing the number of FRβ-expressing macrophages and cathepsin K-positive cells. CONCLUSIONS Intra-articular administration of an immunotoxin to FRβ is effective for improving rat antigen-induced arthritis.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Histopathological changes of the antigen-induced chronic arthritis in the knee joint of the rabbit

Background and Objectives: The cause and pathophysiology of rheumatoid arthritis has not been fully understood and an experimental model of this disease is essential for research on the problem. In this research study, establishment and histopathological changes of chronic arthritis due to intra-articula...

متن کامل

Histological assessment of intera articular injection of 90Y- hydroxyapatite radiocolloid in enrofloxacin induced rheumatoid arthritis in rat models

Histological assessment of intera articular injection of 90Y- hydroxyapatite radiocolloid in enrofloxacin induced rheumatoid arthritis in rat models   Introduction: Rheumatoid arthritis (RA) is one of the most common and disabling diseases in societies that causes chronic synovial inflammation and joint damages. Several pharmaceutical and non-pharmaceutical treatments of RA have been developed...

متن کامل

The Effect of Intra-Articular Injection of Two Anti TNF Drugs on Histopathology and Effect of Local Infusion of these Drugs on Blood Flow of Chronically Inflamed Joints in Rabbit

Background & Aims: The anti TNF drugs are new line treatment for articular inflammatory diseases which are used systemically, but due to expensiveness and some systemic adverse effects have limited usage. The aims of this study were to investigate the effect of intra-articular (local) injection of Etanercept and Infliximab as two anti TNF drugs on histopathology and also due to the important ro...

متن کامل

Effect of Angiotensin II on Blood Flow in Acute and Chronically Inflamed Knee Joints of Rabbits: The Role of Nitric Oxide

Background: Angiotensin converting enzyme (ACE) upregulation in stromal cells of joints affected by rheumatoid arthritis may lead to higher tissue angiotensin II that is a vasoconstrictor and mitogen factor. To date, the role of angiotensin II on regulating blood flow in inflamed joints has not been studied. Methods: Acute and chronic joint inflammation was induced in rabbits by intra-articular...

متن کامل

Experimental Study on Protective Role of NSAID on Articular Cartilage Destruction in Septic Arthritis

Background: Surgical drainage and antibiotic therapy are the cornerstones of treatment protocols in septic arthritis; however, in some circumstances, the diagnosis and initiation of treatment may be retarded by slow disease progression or the time when the patient’s condition precludes early surgery. Therefore, it is beneficial to find ways to reduce the amount of articular injury. This study a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 14  شماره 

صفحات  -

تاریخ انتشار 2012