Release of eosinophil chemotactic factor(ECF)from murine bone marrow derived cultured mast cells was examined. As the indicator cells for in vitro chemotaxis assay, eosinophils were obtained from bone marrow of cyclophosphamide-treated and Toxocara canis-infected mice. When cultured mast cells were stimulated with calcium ionophore A23187 or IgE-antigen, they released ECF as well as β-hexosaminidase. ECF-release was not observed when they were stimulated with compound 48/80. Freeze-thawed extract of cultured mast cells contained β-hexosaminidase but no ECF activity, showing that the ECF is newly synthesized after stimulation. ECF was even spontaneously released when cultured mast cells were incubated for more than 30 min at 37゜C. The ECF released from cultured mast cells was a low molecular weight substance(less than 1300 Dalton), and was resistant to digestion with carboxypeptidase. The ECF was extractable into chloroform-methanol(2:1)at acidic pH. Judging from these physicochemical characteristics, ECF released from cultured mast cells may be an arachidonic acid metabolite.

View full abstract

The characteristics of cell components in BALF were examined in three groups of 104 patients with bronchial asthma, classified by clinical symptoms. 1. The frequency of neutrophils in BALF was significantly higher in patients with hypersecretion type(Ib)and in cases with bronchiolar obstruction type(II)than in cases with simple bronchoconstriction type(Ia). 2. A significantly higher proportions of neutrophils in BALF was observed in atopic asthmatics with type Ib than in non-atopic asthmatics with type Ib. 3. More frequency with moderate or high grade of eosinophilia in BALF were observed in cases with type Ib, whether they were atopic or non-atopic type. 4. More frequency with moderate or high grade of neutrophilia in BALF were observed in atopic cases with Ib and in both topic and non-atopic cases with II. 5. Cases with moderate and high grade of both eosinophilia and neutrophilia in BALF were more frequent in atopic cases with Ib. The results suggest following-1) both eosinophils and neutrophils participate in hypersecretion of type Ib in atopic cases, and only eosinophils in non-atopic cases. 2) Neutrophils participate in bronchiolar obstruction of type II, whether they are atopic or non-atopic cases.

View full abstract

The roles of T cells in in vitro IgM-RF production were examined utilizing two different polyclonal B cell stimulators, Staphylococcus aureus Cowan I(SA)and immobilized mAb to the CD3 molecular complexes(64.1). In cultures stimulated with SA, T4 cells alone but not T8 cells alone could support IgM-RF production. This function of T4 cells could be replaced by IL2 alone or factors generated from mitogen activated T cells(TF). Moreover, when IL2 was supplemented to the cultures, T8 cells as well as T4 cells enhanced the IgM-RF production. Treatment of the T cell subsets with mitomycin C decreased or abrogated the helper function along with a decrease in IL2 production by the T cell subsets in SA stimulated cultures. By contrast, in cultures stimulated with immobilized anti-CD3, T4 cells that had been treated with mitomycin C could induce production of large amounts of IgM-RF, whreas control T4 cells as well as control T8 cells suppressed IgM-RF production. These results indicate that the regulatory functions of T cells in IgM-RF production might be different depending upon the nature of sitmulation signals.

View full abstract

To determine whether neutrophils are involved in airway hyperresponsiveness after ozone exposure, we studied the effect of neutrophil depletion by cyclophosphamide treatment on ozone-induced airway hyperresponsiveness in seven dogs. Airway responsiveness to inhaled methacholine was determined by modified Astograph(7 Hz oscillation method), and the numbers of neutrophils in the peripheral blood, total cell counts and differential cell counts in BALF were measured before and after ozone exposure, and after ozone exposure of dogs undergoing cyclophosphamide treatment. Ozone exposure was carried out for 2hrs at an ozone level of 3.07±0.01ppm(mean±SE), and cyclophosphamide(10mg/kg)was given intravenously daily for five days starting six days before ozone exposure. There was a significant increase in airway responsiveness to inhaled methacholine after ozone exposure in the seven dogs(<0.001), and the numbers of neutrophils in the peripheral blood and the neutrophil counts in BALF increased significantly after ozone exposure(<0.01). After ozone exposure of dogs undergoing cyclophosphamide treatment, the numbers of neutrophils in the peripheral blood decreased significantly(<0.001) and the neutrophil counts in BALF did not increase, but the airway responsiveness to inhaled methacholine increased significantly (<0.01). There was no significant correlation between the degree of the increase in airway responsiveness and the degree of the increase in neutrophil counts in BALF after ozone exposure. These results suggest that neutrophil infiltration into the airway is not necessary for an increase in airway responsiveness after ozone exposure in dogs.

View full abstract

To characterize the antagonistic action of KC-404, an anti-asthmatic agent, against the tachykinin-mediated bronchoconstriction, we studied the effect of this drug on the contractile responses of rabbit tracheal smooth muscle to neurokinin A(NKA) and substance P(SP)under isometric conditions in vitro. Addition of KC-404 relaxed the tracheal rings precontracted with NKA and SP in a dose-sependent fashion but had only a small effect on the contractile responses to acetylcholine and histamine. This inhibitory action of KC-404 was likewise noted even in the presence of atropine. In addition, each of NKA and SP at a concentration insuffcient to alter the resting tone enhanced the contractile response to electrical filed stimulation, an effect that was dose-dependently attenuated by the subsequent application of KC-404. These results suggest that KC-404 may antagonize the bronchocontrictor actions of tachykinins by interacting with their specific receptors on smooth muscle cells as well as on cholinergic nerve terminals in the aiway.

View full abstract

The first patient with alder(Alnus sieboldiana Matsumura)pollinosis in Japan visited our clinic in April 1987. The patient was a 54 year old housewife who had lived in Kobe at the foot of Mt.Rokko since 1972, and had been suffering from the pollinosis for three years. In 1988, prevalence studies of A. sieboldiana in densely planted areas close to the Patient's house were performed using pollen count, immunological examinations and a population survey by questionnaire. A remarkably high prevalence rate of the pollinosis was demonstrated.

View full abstract

Rheumatoid arthritis(RA)patients were investigated for relationships between the concentrations of various plasma opioid peptides(β-endorphin(β-end), methionine-enkephalin(Met-enk), leucine-enkephalin(Leu-enk)and the lymphocyte subsets, serum immunoglobulins, the patient's mood or emotion, and the RA activity. A mental state and patient mood were assessed by the Cornell Medical Index(CMI)and the Face Scale. RA activity was expressed by Lansbury's index. The plasma Met-enk concentration was correlated significatly with the %Leu11^+ and %Leu11^+ Leu7^+ cells. The plasma Leu-enk concentration also correlated significantly with the %Leu2a^+ Leu15^- cells. The plasma Leu-enk concentration and pain score were higher while the %Leu11^+ Leu7^- cells was lower in proportion of the degree of neurosis of the RA patient as indicated by the CMI. The plasma Met-enk concentration, the %Leu2a^+ Leu15^-, IgG, pain score and lansbury's index were significantly higher in the group of RA patients whose facial expression was more severe. These findings suggest that enkephalins have some relationship with the patient's mood and immunologic functions, and that enkephalins have possibility of exerting indirect effects on RA.

View full abstract

Serum levels of gamma interferon(IFN-γ) were determined by a sandwich radioimmunoassay in 45 patients with Kawasaki Disease(KD), 14 with measles, 3 with streptococcal infection. 17 with anaphylactoid purpura, 6 with various vasculitis and also in 10 healthy children. Serum levels of IFN-γ were seen to increase during the acute phase of KD and measles. In addition, serum levels of tumor necrosis factor(TNF)and interleukin 2 receptor(IL-2R)were measured simultaneously in 45 patients with KD. In KD patients with coronary-artery lesions(CAL), the percentage of positive cases for TNF(≧10 units/ml), IL-2R(≧1056 units/ml)and IFN-γ(≧0.3 units/ml)was higher than that in patients without CAL. Several cytokines in association with activated monocytes/macrophages and T lymphocytes were detected in the serum during acute KD. These results suggest that aggressive activation of immuno-competent cells cevelops in KD involved CAL.

View full abstract