Two forms of monocyte chemoattractant protein-1 (MCP-1), MCP-lα and β have been purified from culture supernatants of either human malignant glioma cell line cells or PHA-stimulated peripheral blood mononuclear leukocytes. MCP-1 is chemotactic for monocytes but not for neutrophils, and appears to be identical to lymphocyte-derived chemotactic factor reported previously by others in an early era of lymphokine research. Amino acid sequence analysis and cDNA cloning have revealed that MCP-1 belongs to a family of proteins characterized by the location of 4 cysteins. Among those, mouse JE which was defined as a clone expressed by PDGF-stimulated fibroblasts has the highest similarity to MCP-1, suggesting that MCP-1 is a human homologue of mouse JE.
Recently human JE has been cloned and found to be identical to MCP-1. Furthermore, human fibroblasts are capable to produce MCP-1 and the production is regulated by PDGF. From these results, it is highly possible that MCP-1 is identical to JE and this protein may play an important role in macrophage infiltration in vivo.

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An involvement of monokines in proliferation of mesangial cells was studied in experimental mesangial cell proliferative glomerulonephritis model and in culture. Anti-rat thyrnocyte serum (ATS) recognized Thy-1.1 (-like) molecules on the glomerular mesangial cells and an intravenous administration of ATS in rats induced glomerular hypercellular lesion 4-7 days later. The glomerular lesion was composed mainly of proliferating mesangial cells as defined by immunofluorescence staining for Thy-1.1 or desmin and less of infiltraing monocytes and lymphocytes as characterized by presence of leucocyte common or Ia antigen.
The promotion of mesangial cell proliferation in the glomeruli of ATS-administered rat kidneys was supported by enhancement of ³H thymidine uptake in the glomerular cells in culture and by increase of Thy-1.1 mRNA content in the glomerular RNA. The glomeruli from the ATS-administered rats released interleukin 1 (IL-1) and tumor necrosis factor (TNF) activities in culture medium and had more IL-1β mRNA than control rat glomeruli. Recombinant human IL-1β and TNF enhanced proliferation of quiescent rat mesangial cells in culture in the simultaneous presence of low concentration of fetal bovine serum or platelet-derived growth factor, as was the case with insulin.
These results indicate that monocytes/macrophages infiltrating in glomeruli with glomerulonephritis could release monokines, such as IL-1 or TNF and these cytokines could promote proliferation of mesangial cells.

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Rat mast cell granules and plasma membrane fractions were obtained from highly purified intact cells by homogenization followed by Percoll and sucrose density gradient centrifugation respectively and immunostained with two types of mouse monoclonal anti-MAG antibodies: IgG antibody recognizing a polypeptide moiety of intact MAG (IgG-P) and IgM antibody recognizing a carbohydrate moiety (IgM-C) . Both intact cells and granule fraction, but not plasma membrane fraction were well stained with IgM-C.
Granule fraction fixed with glutaraldehyde showed a ring-like pattern by immunostaining with IgM-C. On the contrary, neither intact cells nor granules and plasma membrane fractions were reacted with IgG-P. Both intact cells and granule fraction treated with chloroform-methanol were also densely stained with IgM-C., indicating that IgM-C positive epitope is present in the granule fraction of the mast cell and shares with a carbohydrate moiety of MAG.

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When heat-killed Propionibacterium aches is intravenously injected into mice and seven days later, a small amount of gram-negative lipopolysaccharide (LPS) is also intravenously injected, most of the mice die of massive hepatic cell necrosis. However, when Lipo prostaglandin E₁ was administered during this experimental induction of acute hepatic failue, the viability of the mice increased and the histological changes of the liver remarkably improved.
These results suggested that Lipo prostaglandin E₁ was effective in our experimental acute hepatic failure model. Since there is no difinite treatment method for fluminant hepatitis at present, Lipo prostaglandin E₁ may be useful as a clinical treatment in future.

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Gastric microcirculatory disturbances induced by intermittent electrical stimuli (irritation) on the gastric artery produced acute gastric mucosal lesions in the rat stomach. In this experimental model, participation of platelet-activating factor (PAF) in granulocyte-endothelium interaction were evaluated.
Laser doppler flowmetry revealed that post-ischemic hyperemia was observed just after the irritation and the flow was significantly decreased after this hyperemic state. Mucosal tissue-type plasminogen activator (t-PA) activity was also elevated just after the irritation and still more increased thirty minutes after the stimuli. Moreover, both luminol-dependent chemiluminescence activity of regional blood sample and myeloperoxidase activity in gastric mucosa were remarkably increased thirty minutes after the irritation. A newly developed PAF-antagonist, CV-6209 attenuated the local fibrinolytic activity, granulocyte-mediated oxidative stress and the alteration of mucosal blood flow, and significantly diminished the gastric ulcer formation.
The present study suggests that PAF may cause the excessive fibrinolytic activity and granulocyte-mediated oxidative stress on mucosal microvasculature during acute gastric ulcer formation.

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To evaluate the prophylactic effect of ranitidine, H₂ blocker, for gastroduodenal mucosal damages in patients with rheumatoid arthritis (RA) and normal volunteers, a randomized placebocontrolled study was conducted whether or not the concomitant administration of ranitidine could reduce the gastroduodenal mucosal damages on short term (2 weeks) NSAIDs.
Ranitidine 150 mg or placebo twice daily plus NSAIDs (diclofenac Na, piroxicam, mefenamic acid) were administrated to 40 RA patients for 2 weeks with an endoscopic assessment on 0 and 14 day. The same randomized clinical trials were also performed in 20 healthy volunteers. Ranitidine/NSAIDs in RA patients group had significantly less gastroduodenal mucosal damages (P<0.002) than the placebo/NSAIDs in patients group and the same tendency was observed in normal volunteers. Gastroduodenal mucosal damages were influenced by smorking habits, alchol intake and coffee consumption in the volunteer group.
It is concluded that rantidine 150 mg twice daily reduced the incidence of gastroduodenal mucosal damages on NSAIDs.

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Histopathological analysis of the synovial tissues from 7 cases of HTLV-1 carriers who had chronic arthritis was performed. Synovial tissues showed villous proliferation to a various degree. Proliferation of synovial stromal cells associated with interstitial edema and proliferation of small blood vessels was observed. Lymphocytic infiltration was rather diffuse without evident lymph-follicle like structures. The most characteristic feature was the presence of atypical lymphocytes with nuclear convolution in the synovial tissues. Immunohistochemical analysis of the synovial tissues revealed infiltration both of CD4 and CD8 positive lymphocytes, accompanied with the expression of HLA-DR antigens on the synovial cells.
These findings suggest that HTLV-1 infection might play an important role in the pathogenesis of the arthritis. Further examination of the function of HTLV-1 infected cells in the arthropathy is necessary.

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Gold sodium thiomalate (GST) markedly inhibited the production of IL-1β by normal mononuclear cells and normal monocytes, and slightly inhibited TNF production by normal mononuclear cells.
Bucillamine, a SH compound, on the other hand, strongly inhibited TNF production by mononuclear cells. These results suggest that the inhibitory effects of GST and Bucillamine on the cytokine production may be one of the mechanisms by which the drugs modify the tissue destruction in rheumatoid arthritis.

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By flow cytometric method with dichlorofluorescin diacetate, we analysed oxidative products of neutrophils in patients with Behcet disease, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and progressive systemic sclerosis (PSS) .
The rate of “primed” cells that produced oxidative products in unstimulated neutrophils was higher in patients than in normal control, but in PMA-stimulated neutrophils, there was no differences in patients and normal control. And there were statistical correlations of the primed cells in unstimulated neutrophils and some markers of disease acitivities. This flow cytometric method could clarify the influence of time and temperature from sampling to assay, and was useful to study the functions of cells.

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