Recent advances in the study of eosinophils, basophil leukocytes and mast cells in allergic inflammation of the airway are summarized, including their chemotaxis, mediator release and function.
Different kinds of chemotactic factors for eosinophil leukocytes are reported. Of them, ECF-A may be the most important in specifity, intensity and the amount released in allergic lesion. On the other hand the chemotactic factor for basophil leukocyte is still not at all understood.
Both eosinophil, basophil leukocytes and mast cells are degranulated and release extracelluraly different kinds of inflammatory mediators as sequences of allergic reaction.
From basophil leukocytes and mast cells, mediators such as histamine, proteoglycan, proteases, hydrolytic enzymes, oxydative enzymes, kinin, eosinophil chemotactic factor, leukotrien C₄ and B₄, thromboxane A₂ and prostaglandin et al. are released; and from eosinophil leukocytes, mediators such as neutral proteases, hydrolytic enzymes, oxidative enzymes, major basic protein, eosinophil cationic protein, eosinophil derived neurotoxin, Charcot Leyden Crystal, leukotrien C₄, prostaglandin E₁ and E₂, platelet activating factor et al. are released.
These mediators produce various pathological conditions, that is, contraction of the smooth muscles, increased permeability of the blood vessels, hypersecretion from the secretory glands, migration of the white cells, and irritation to the nerves. In allergic rhinitis, histamine and leukotrien may play the most important role in these inflammatory processes.

View full abstract

Granules were isolated from sonicated rat mast cells on Percoll gradient and incubated with [γ³²P] ATP in the presence of Mg²⁺ and exogenous diphosphoinositide. After stopping the reaction, lipid extraction of the intact membrane granules was performed with acidic medium and phospholipids were separated by thin layer chromatography on 1% (w/v) oxalic acid and potassium oxalate impregnated silica gel plates. Considerable amounts of radioactivity were found to be incorporated into TPI on both plates. Extensive washing of the granules did not significantly affect the ³²P incorporation into TPI. The radioactivity in TPI was associated with the granule themselves and it is apparent that TPI is produced in rat mast cell granule.

View full abstract

Carboxyethylgermanium sesquioxide, Ge-132 was investigated for its effect on the expression of HLA-DR ant·pens or IgG-Fc receptors (FcRl) on human peripheral blood monocytes and a human myelogenous leukemia cell line U937 in culture. Ge-132, when added in the cultures of either purified peripheral monocytes or U937 cells, did not produce any significant effect on expression of either HLA-DR antigens or FcRl on the cell. The peripheral blood mononuclear cells (PBMC) when being incubated with Ge-132 (800μg/ml), however, produced a factor inducing augmentation of HLA-DR and FcR expression on the monocytes or U937. Pretreatment of this PBMC culture fluid with pH2.0 or specific antiserum against human interferon γ (IFNγ) resulted in a marked reduction of both HLA-DR and FcR-inducing activities, suggesting that a major factor induced by Ge-132 in the PBMC may be IFNγ. These results indicate that Ge-132 stimulates PBMC to produce a soluble factor (IFNγ), which in turn augments the expression of HLA-DR antigens and FcRl on the cell of myelogenous or macrophage series.

View full abstract

A monoclonal antibody has been produced in the mouse system using copper-zinc superoxide dismutase (Cu, Zn-SOD) isolated from human blood. According to ELISA, the antibody was of the immunoglobulin Gl class and slightly cross-reacted with bovine and canine Cu, Zn-SOD but not with human serum albumin, α-globulin β-globulin and γ-globulin. Immunohistochemical analysis showed the localization of Cu, Zn-SOD in the hepatocytes, gastric glandular cells, colonic absorptive epithelial cells, ciliated bronchiolar cells, cells lining renal tubule in the nephron, Langerhans islet and exocrine centro acinus cells in the pancreas and neurons of the central nervous system.

View full abstract

Possible effects of sera from patients with collagen diseases on human EC proliferation in vitro were investigated. EC from umbilical vein were incubated with 20% test serum for 3 days and uptake of ³HTdR by EC was determined. Ten out of 29 PSS and 4 out of 18 Raynaud disease sera remarkably suppressed EC proliferation (below 10% of normal control sera) . On the other hand, only one out of 17 RA sera and none of 14 SLE sera possessed such effect. By morphological observation, this suppressive effect revealed to be cytotoxicity against EC.
The experiment with fractionated serum on Sephadex G-200 gel suggested that this cytotoxic factor eluated with albumin. Possible contribution of this factor to the pathogenesis of vascular damage and Raynaud phenomenon in PSS was discussed.

View full abstract

Ischemia by reduction of gastric mucosal blood flow has been proposed an explanation for the formation of stress ulcer. However, the mechanism that ischemia produces mucosal lesions remains uncertain.
Recently, the role that free radicals may plays in the ischemic-induced tissue injury have received attention.
So, in this study we investigated whether free radicals play a role in the formation of stress ulcer and furthermore whether iron plays an important role in the production of free radicals. To achieve this goal, we adapted water-immersion stress method and use various scavengers (superoxide dismutase, catalase), allopurinol, deferoxamine as chelator of ferric iron.
Allopurinol, inhibitor of xanthine oxidase, significantly reduced gastric lesions at the inhibitory rate of 80%.
When SOD and catalase were administered at the same time, the inhibitory rate was 25%. When SOD was only administered, the effect appeared at 5 hrs during its experimental course (7 hrs) . This result seemed to be related in the half time of SOD in vivo.
On the other hand, production of hydroxyl radical depends on“iron-catalysed Harber-Weiss reaction”. When deferoxamine was administered, the inhibitory rate was 45%.
These data indicated that free radicals plays a role in the formation of stress ulcer and that hydroxyl radical is more important, furthermore that ferric iron plays an important role in the production of free radical.

View full abstract

This recent study examined the effect of P-FN on CL response and O^-₂ production induced by stimulation of neutrophil mem-brane with zymosan, n-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, Ca²⁺ ionophore A 23187 and cytochalasin E. The relative intensity of luminol-dependent CL (LDCL) response was evaluated by ATP photometry, and O^-₂ production was spectrophotometrically measured by ferricytochrome C reduction in reaction mixtures with and without P-FN.
The results showed that both LDCL response and O^-₂ production of neutrophil were enhanced by the presence of P-FN in a dose-dependent manner. But P-FN alone could not induce LDCL response and O^-₂ production. From these results, it is suggested that P-FN may supplement respiratory burst of neutrophil.

View full abstract

Superoxide dismutase (SOD) is produced in every human cells to prevent from the auto-oxidative damages by increasingly released oxygen-intermediates. We tried to treat with liposomal SOD 9 patients with intractable diseases, 3 PSS, 1 PM, 1 PSS+DM, 1 SLE+PM, 2 Behçet's disease and 1 paraquart intoxication. The patients were administered liposomal SOD at 2.5 mg/body 3 times in a week for one or two months. Two weeks after the administration, 4 patients with PSS and PM were significant improvement in their clinical symptoms such as palpitation and shortness of breath, and also % VC incresed to nearly normal range. An another patient with SLE plus PM who had chest oppression feeling due to myocardiopathy was also improvement. However liposomal SOD was not effective in a case of Behçet's disease. We think that liposomal SOD may be useful for intractable diseases, particularly when conventional therapies have failed.

View full abstract

The activation of complement components in the complement cascade plays an important role in the pathophysiology in anaphylactic shock, serious infection and massive tissue damage. Two anaphylatoxins are derived from complement 3 and 5 of the cascade and are called C3a and C5a, respectively.
In the present investigation we measured plasma C3a and C5a in rabbits with aspiration pneumonia or air embolism by the radioimmunoassay method.
1) Plasma complement C3a and C5a levels reached to the maximum 7 minutes after the aspiration pneumonia induced by pH 2 HCl instillation and returned to the control level 30 minutes after in rabbits.
2) Plasma complement C3a level reached to the maximum 7 minutes after the air embolism and stayed in higher level for 60 minutes, however plasma complement C5a level reached to the maximum 5 minutes after the procedure and returned to the control level in rabbits.
3) In these two experimental models of ARDS, aspiration pneumonia and air embolism, plasma complement C3a and C5a levels showed a significant increase and reached to the maximum 5 to 7 minutes after the procedures.

View full abstract

When a macrophage was stimulated with fMet-Leu-Phe, arachidonic acid was released. The release of arachidonic acid was inhibited by the treatment of Syosaiko-to, dose-dependently. And the soluble fraction separated from macrophages that were treated with 100μg/ml of Syosaiko-to inhibited the release of [¹⁴C] -arachidonic acid resulting from the incubation with porcine pancreatic phospholipase A2 and α-parmitoyl-β- [¹⁴C] -arachidonyl phosphatidylcholine. From these findings, it was suggested that Syosaiko-to had an inhibitory effect on arachidonic cascade and this effect was due to the induction of phospholipase A2 inhibitory protein.

View full abstract