Hiroomi Ogata

The role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of collagen-induced arthritis in rats

Collagen‐induced arthritis was produced in rats by intradermal immunization with type II collagen and the expression and production of monocyte chemoattractant protein‐1 (MCP‐1) were examined by immunohistochemistry, enzyme‐linked immunosorbent assay (ELISA), and Northern blot analysis. Two to three weeks after the immunization, the hindfeet showed swelling and redness, followed by the development of severe arthritis, particularly in the ankle joints. During this period, prominent infiltration of neutrophils and macrophages was observed. Sandwich ELISA and Northern blot analysis revealed that MCP‐1 concentrations in the joint lavages and MCP‐1 mRNA levels in the joint tissues both peaked at 2 weeks after the immunization. By immunohistochemistry, various types of cells, particularly neutrophils, macrophages, synovial cells, and vascular endothelial cells, stained positively for MCP‐1. Finally, injection of a neutralizing monoclonal antibody against rat MCP‐1 significantly decreased the number of exudate macrophages in the lesions and reduced the ankle swelling by about 30 per cent compared with controls. These results suggest that MCP‐1 plays a critical role in this model in the recruitment of monocytes and in the development of arthritis.

Monocyte chemoattractant protein-1 in the intervertebral disc. A histologic experimental model.

Study Design. Monocyte chemoattractant protein‐1 was investigated in an experimental rat model using immunohistochemistry. Objective. To ascertain the precise mechanism of macrophage recruitment in the early phase of disc resorption. Summary of Background Data. In previous studies, many investigators reported that disc herniation was resorbed by monocytic phagocytosis. However, how the recruitment of monocytes was triggered is still unknown. Methods. The autologous intervertebral discs from tails of Wistar rats were subcutaneously implanted into the abdomen. These discs were obtained on days 2, 3, 7, and 14 after implantation and were used for immunohistochemical study and for quantitative analysis of monocyte chemoattractant protein‐1 by sandwich enzyme‐linked immunosorbent assay. Results. Monocyte chemoattractant protein‐1‐positive granulocytes and macrophages were observed surrounding the intervertebral disc, and monocyte chemoattractant protein‐1‐positive disc chondrocytes were observed in the nucleus pulposus and the inner anulus fibrosus on day 3. By day 7, monocyte chemoattractant protein‐1‐positive and TRPM‐3‐positive macrophages appeared in the granulation tissue, and some of these cells invaded the nucleus pulposus and inner anulus fibrosus. The concentration of monocyte chemoattractant protein‐1 was highest on day 3. Conclusion. Intervertebral disc chondrocytes have chemotactic properties and play an active role in the recruitment of monocytes involved in disc resorption.

molecular Cloning of the Guinea Pig GRO Gene and Its Rapid Expression in the Tissues of Lipopolysaccharide–Injected Guinea Pigs

Background: CXC chemokines, IL–8 and GRO, play a role in the recruitment of neutrophils in the human. The functional orthologues in the rat and mouse are CINC/KC and MIP–2. The lack of IL–8 made these animals less useful to study the role of IL–8 and GRO. Methods: Guinea pig (gp) cDNA libraries were screened for GRO and IL–1β. A gp genomic library was screened with a gpGRO cDNA probe. Expression of gpIL–8, gpGRO, gpTNFα, and gpIL–1β was investigated by Northern analysis and/or by in situ hybridization. Results: Two gpGRO cDNAs, a 3.0–kb gpGRO genomic DNA, and a gpIL–1β cDNA were cloned. gpGRO and gpIL–8 mRNA were detected in different tissues including lungs 1 h after intraperitoneal injection of lipopolysaccharide (LPS) into guinea pigs. gpGRO, gpIL–8, gpTNFα, and gpIL–1β expression peaked at 3 h in the lungs. Both gpGRO and gpIL–8 mRNA were detected in the cells in alveolar spaces and bronchial epithelial cells. However, gpGRO mRNA, but not gpIL–8, was also expressed in endothelial cells and vascular smooth muscle cells. Conclusions: gpGRO and gpIL–8 mRNA rapidly accumulated in the lungs of guinea pigs after LPS injection. Expression of gpIL–8 and gpGRO mRNA appeared to be independent from TNFα– or IL–1β–stimulation in this model. A high level expression of gpGRO in vascular cells suggest an important role of GRO in the sequestration of neutrophils and multi–organ injuries induced by LPS. The guinea pig will provide an excellent model to study the roles of IL–8 and GRO, important inflammatory mediators in the human.

Arthroscopic Debridement for Lateral Type Gonarthrosis

Between 1989 and 1991, we performed arthroscopic debridement for 10 patients (12 joints) with lateral type gonarthrosis. Fibrillation of chondral-bone was seen in 7 joints, erosion in 3 joints and large chondral-bone loss in 2 joints. Six of the 12 joints had a degenerative tear of the lateral discoid and the rest had severe degenerative tears of the lateral meniscus. All joints had a partial menisectomy with 2 joints additionally requiring drilling for chondral bone ulceration. Clinical evaluation was made using the Japanese Orthopaedic Assosiation (JOA score) criteria, with good results obtained. (Average score improved from 86.7±5.1 to 97.9±6.9, and the mean follow-up period was 30.0 months)