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T Ohtoshi

Publications and source records attributed to T Ohtoshi.

At least 37 records · Page 2Linked to original sources
PubMed1994

Cefotiam-induced IgE-mediated occupational contact anaphylaxis of nurses; case reports, RAST analysis, and a review of the literature.

Cefotiam (CTM) is one of the most popular cephem antibiotics in Japan. Recently we experienced two cases of nurses with CTM-induced contact anaphylaxis. When they were preparing drip infusions of antibiotics or working around other nurses doing so, they suddenly fell into shock with other symptoms such as flushing, urticaria, abdominal distress, vomiting, dyspnoea and/or loss of consciousness. The symptoms never occurred after they avoided exposure to CTM. Passive cutaneous or open patch tests were positive for CTM. Histamine release was induced by CTM from washed leucocytes. RAST analysis using CTM-human serum albumin-coupled discs showed high % RAST count, suggesting that these reactions were mediated by IgE antibodies. A RAST inhibition test suggested that the methyl-thiotetrazole side-chain was the main antigenic determinant. Both patients had hand dermatitis that had appeared preceding the episodes of anaphylaxis. Although the dermatitis had been resistant to treatments, it also disappeared after they avoided exposure to CTM. It seemed likely that it was also induced or exacerbated by CTM and facilitated the penetration of CTM to cause anaphylaxis. The literature is also reviewed.

Adult↗
PubMed1994

Endotoxin and pro-inflammatory cytokines stimulate endothelin-1 expression and release by airway epithelial cells.

Endothelin is a potent bronchoconstrictor peptide first identified as a novel vasoconstrictor produced by vascular endothelial cells. Recent reports suggest that airway epithelial cells are also capable of releasing this active peptide. To investigate the regulatory mechanism of endothelin expression, we studied the effects of endotoxin and pro-inflammatory cytokines such as interleukin-1 and tumour necrosis factor on the expression and release of endothelin-1 by airway epithelial cells. Both endotoxin and the cytokines stimulated endothelin-1 release by human bronchial epithelial cells. Northern blot analysis showed increased expression of preproendothelin-1 mRNA by these factors. These results suggested that airway epithelial cells might play a role in the local airway smooth muscle tone through the production of endothelin, which might be upregulated by inflammatory products in the airways.

Aged↗
PubMed1994

Dexamethasone inhibits basophil migration.

Glucocorticoids have been shown to inhibit the local accumulation of basophils during the allergen-induced late-phase reaction (LPR). Since migration is an essential step in the recruitment of basophils from the circulation, we examined whether the widely used glucocorticoid, dexamethasone (DEX), directly acts on basophils to inhibit the migration caused by C5a, interleukin (IL)-3, and IL-8. When purified basophils were preincubated with various concentrations of DEX, a dose-dependent inhibition was observed; DEX at concentrations as low as 1 nM reduced the number of migrated basophils by 30-40%; at higher concentrations, it showed a slightly stronger inhibitory effect. There was no significant difference in the effect of DEX on the migration caused by the three chemoattractants. The action of DEX took place rapidly; apparent inhibition was observed even when migration was initiated without preincubation. Although the inhibitory effect of this agent was not reversed when DEX was removed by washing, the inhibition was not mediated by the toxicity as measured by the trypan-blue exclusion test. These results indicate that the in vivo blocking effect of glucocorticoids on basophil accumulation during LPR is mediated in part by direct action to inhibit the migration of basophils.

Basophils↗
PubMed1994

[Cytokine production by human airway epithelial cells and its modulation].

There is increasing evidence that airway epithelial cells play an active role in allergic inflammation, including bronchial asthma. We showed that human airway epithelial cells in culture release GM-CSF, G-CSF, M-CSF, IL-6, and IL-8, using a serum-free culture system. These cytokines are known to modulate the bioactivities of inflammatory cells that accumulate at the site of inflammation. Among them, GM-CSF, IL-8, or both may be important because they influence the bioactivities of eosinophils, which are characteristic of allergic inflammation. Here we report on the effects of air pollutants such as suspended particulate matter and diesel exhaust particulates on release of cytokines from airway epithelial cells. All air pollutants we tested stimulated epithelial cells to release GM-CSF. These results suggest that one cause of the recent increase in the prevalence of allergic disorders is direct stimulation of airway epithelial cells by air-pollutants. Furthermore, anti-inflammatory agents such as steroids and anti-allergic drugs were found to suppress the release of GM-CSF from airway epithelial cells in vitro.

Air Pollutants↗
PubMed1993

Growth inhibition of human lung cancer cell lines by interleukin 6 in vitro: a possible role in tumor growth via an autocrine mechanism.

It has been considered that growth of human lung cancer cells, like other malignant cells, is positively and negatively regulated by a variety of growth factors via autocrine as well as paracrine mechanisms. The autocrine mechanism is considered to be important in the autonomy of proliferation of cancer cells. Recently, the role of autocrine growth-inhibiting factors such as transforming growth factor beta attracts special attention for better understanding of growth regulation of malignant cells. Here, we have demonstrated that a multifunctional cytokine interleukin 6 (IL-6) had an inhibitory effect on the proliferation of human non-small cell lung cancer cell lines, as shown by the growth accelerating effect of the specific anti-IL-6 antibody as well as the effect of exogenously added IL-6. Moreover, IL-6 can be expressed and released by human lung cancer cells, and these cells had specific IL-6 receptors on their cell surfaces, suggesting an autocrine mechanism. The growth-inhibitory effect of IL-6 was additive to that of transforming growth factor beta, and could not be neutralized by the addition of anti-transforming growth factor beta antibody. These results suggested that IL-6 may function as another class of autocrine growth-inhibiting factor in the growth regulation of human lung cancer. Relatively lower IL-6 sensitivity of these cells than noncarcinogenic human bronchial epithelial cells also suggested that escape from growth regulation by inhibitory factors such as IL-6 could be involved in lung cancer oncogenesis.

Adenocarcinoma↗
PubMed1993

Modulation of human basophil histamine release by insulin-like growth factors.

Several lines of evidence indicate that basophils play an active pathogenic role in the late-phase reaction. Inasmuch as various cytokines are produced locally by activated cells of the immune system during late-phase reaction, "priming" of basophils by cytokines has become an area of active study over the last few years. We studied the effect of insulin-like growth factor (IGF)-I, shown to be active on immature and mature hemopoietic cells, on histamine release from human basophils. IGF-I enhanced histamine release initiated by anti-IgE, calcium ionophore A23187, and phorbol ester in a dose-dependent fashion (ED50: 300-600 pM), although IGF-I had little or no effect on the release caused by FMLP and C5a. The priming effect of IGF-I took place rapidly and reached plateau levels in 15 min. IGF-II and insulin, both of which have high amino acid sequence homology with IGF-I, also primed basophils. The order of enhancing potencies was IGF-I > IGF-II > insulin; IGF-I was 10-fold more potent than IGF-II and 250-fold more potent than insulin. Although specific receptors for each factor have been identified, blocking experiments using a mAb against IGF-I receptor showed almost complete abolishment of the enhancing effect of these factors, indicating that the enhancing effect is exhibited via the IGF-I receptor. Inasmuch as IGF-I has been shown to be produced by alveolar macrophages, fibroblasts, and nasal polyps, these results indicate that IGF may regulate allergic reactions in vivo by enhancing histamine release from basophils.

Basophils↗
PubMed1993

Lipopolysaccharide induces expression of granulocyte/macrophage colony-stimulating factor, interleukin-8, and interleukin-6 in human nasal, but not lung, fibroblasts: evidence for heterogeneity within the respiratory tract.

Fibroblasts play an indirect augmenting effector role in the inflammatory response by releasing growth and differentiation factors and other inflammatory mediators after activation by inflammatory cytokines such as interleukin (IL)-1, but whether direct activation occurs by exogenous agents such as endotoxin (lipopolysaccharide, LPS) remains controversial. Using a number of primary human airways tissue-derived fibroblast lines, we demonstrate that in contrast to IL-1 alpha, LPS significantly induced gene expression and production of granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-8, and IL-6 only in nasal but not bronchial or lung tissue-derived fibroblasts. Enhanced expression was dose- and time-dependent, and the minimal stimulatory dose was 10 ng LPS/ml. Polymyxin B entirely abrogated increased cytokine expression by LPS. Actinomycin D treatment largely inhibited expression, and LPS markedly increased an IL-6 gene promoter-driven luciferase reporter response in transfected nasal fibroblasts, suggesting enhanced expression may involve transcriptional regulation. Secondary protein or IL-1 synthesis requirement seemed unlikely since cycloheximide superinduced LPS-stimulated cytokine expression and anti-IL-1 alpha/beta antibodies failed to abrogate the response. Thus our data show that GM-CSF, IL-8, and IL-6 are directly inducible in nasal fibroblasts by LPS, and establish heterogeneous responsiveness to LPS by different fibroblast populations in the airways.

Animals↗
PubMed1992

Interleukin 6/B cell stimulatory factor-II is expressed and released by normal and transformed human bronchial epithelial cells.

Airway epithelial cells have a potential to participate in local immune and inflammatory responses via releasing biologically active compounds. We studied the expression and release of interleukin 6 (IL-6), a multifunctional cytokine possibly involved in tissue immune responses. Primary culture of normal human bronchial epithelial cells and its transformed cell line BEAS-2B released significant amount of biologically and immunologically intact IL-6 into media. A protein synthesis inhibitor cycloheximide abolished the IL-6 release, suggesting a de novo synthesis. Northern blot analysis demonstrated the expression of the specific IL-6 mRNA. Human bronchial epithelial cells can produce IL-6 and contribute to the local activity of IL-6, suggesting that these cells may play a role in the regulation of airway immune responses.

Antibodies, Monoclonal↗
PubMed1992

Human upper airway structural cell-derived cytokines support human peripheral blood monocyte survival: a potential mechanism for monocyte/macrophage accumulation in the tissue.

A central feature of chronic airway inflammation is accumulation of monocyte/macrophages in the tissue. It is well known that circulating monocytes are short-lived cells whereas tissue macrophages are longer-lived cells. One mechanism that may account for accumulation of inflammatory cells includes enhanced survival and/or differentiation of these cells. Recent studies imply that signals released by tissue structural cells may be crucial in these events. To investigate this notion, human blood monocytes were cultured with either culture medium alone as a control, human nasal epithelial cell-conditioned medium (EpCM), or fibroblast-conditioned medium (FCM) for more than 1 wk. Survival of monocytes in medium alone was 17% at day 7, whereas survival of those cultured with 50% of EpCM or FCM was 62% and 64%, respectively. The effect of EpCM and FCM was dose dependent. Preincubation of either conditioned medium (CM) with an antibody against granulocyte/macrophage colony-stimulating factor (GM-CSF) or an antibody against macrophage colony-stimulating factor (M-CSF) resulted in a partial abrogation of the survival-enhancing effect, to an average of 50% and 30%, respectively. Complete inhibition was obtained by preincubation of the CM with a combination of both antibodies. The effect of CM represented true survival because CM only induced a low profile of [3H]thymidine incorporation and, furthermore, less than 0.3% of the cells cultured with CM underwent DNA synthesis as assessed by autoradiography. In addition, ultrastructural observations demonstrated that most monocytes cultured with either CM but not with control culture medium assumed ultrastructural features of macrophages by day 8 of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation↗
PubMed1991

Topical thrombin-induced IgE-mediated anaphylaxis: RAST analysis and skin test studies.

Bovine topical thrombin (BTT) is a heterologous plasma thrombin concentrate that has been frequently used for the hemostasis since the 1940s. Recently, three patients in Japan went into shock after the topical application of BTT at lesion sites, and two of these patients had received BTT repeatedly. The clinical symptoms and the increased anti-BTT percent RAST counts suggest that these reactions were shock mediated by anti-BTT IgE antibodies. The RAST-inhibition analysis suggested that the antigenic substance(s) were bovine-specific moiety(ies) mainly involved in the contaminant rather than bovine thrombin itself. The skin tests were studied to predict such allergic reactions. The intracutaneous test provoked nonspecific reactions even at the low concentrations of BTT. The prospective study on the predictive value of the prick test with 1000 U/ml (1 mg/ml) of BTT in 192 patients suggested that it is useful to detect highly sensitive patients. In addition, the increased levels of anti-BTT IgE antibodies in patients 1 month after the single administration of BTT suggested the immunogenicity of the topical application of BTT.

Administration, Topical↗
PubMed1991

Structural cell-derived cytokines in allergic inflammation.

Based on observations of fluctuations in progenitors for inflammatory cells during allergic responses, we have proposed that a primary determinant of allergic inflammation involves microenvironmental influences on hemopoietic cell differentiation and phenotype; in addition, as a corollary of this, inflammatory cell burden is proposed as an important indicator of the severity and pattern of the inflammatory process in allergy. The studies outlined here focus on the effects of epithelial-cell- and fibroblast-derived cytokines on granulocytic and monocytic cell differentiation and activation in models involving allergic reactions in the upper and lower airways. Pure cultures of nasal or bronchial epithelial cells or fibroblasts are observed to give rise to cytokines important in inducing the differentiation of basophils, eosinophils, neutrophils and monocyte/macrophages. Gene expression, production and secretion of granulocyte/macrophage-colony-stimulating factor, interleukin-6 (IL-6) and IL-8 can be demonstrated in vitro and in vivo. Up-regulation of gene expression and production of these cytokines, which are important in inducing basophil, eosinophil and neutrophil/macrophage differentiation in several assays, is seen with IL-1 and the neuropeptide substance P; conversely, inhibition of cytokine production by structural cells is observed after pretreatment with corticosteroids in vitro, paralleling in vivo effects. Other modulatory effects also examined include: antiallergic compounds, which may affect posttranscriptional events in cytokine production, and heavy metal ions, which can also induce changes in gene expression. Structural-cell-derived extracellular matrices appear also to be important both in mast cell differentiation and in macrophage cytokine gene expression, both of which potentially feedback upon chronic allergic inflammatory processes, leading to their perpetuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗
PubMed1991

Human upper airway epithelial cell-derived granulocyte-macrophage colony-stimulating factor induces histamine-containing cell differentiation of human progenitor cells.

Nasal polyps and allergic rhinitis are upper airway inflammatory conditions characterized by increased numbers of eosinophils and metachromatic cells in the epithelial layer of the nasal mucosa. The objective of the current studies was to investigate the potential contribution of epithelial cells to the accumulation of inflammatory cells in the tissue. We have established pure cultures of human upper airway epithelial cells from normal and inflamed nasal polyps and allergic rhinitis tissue and examined the ability of conditioned medium from these cells (EpCM) to induce differentiation of human hemopoietic progenitors in vitro. We show that, under appropriate culture conditions, EpCMs, particularly those from cells derived from inflamed tissues, induce histamine-containing cell differentiation of cells of the human HL-60 myeloid leukemia cell line. These EpCMs also induce the emergence of both eosinophil/basophil and granulocyte/macrophage colonies in methylcellulose cultures of human peripheral blood mononuclear cells. We also show that CMs from epithelial cells derived from inflamed tissues contain greater amounts of granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to CMs from normal epithelial cells. Finally, we show that the histamine-containing cell differentiation of HL-60 cells as well as the colony growth induced by EpCM can be fully inhibited by preincubating this CM with a monoclonal neutralizing antibody to human GM-CSF. These studies: (a) illustrate the ability of human upper airway epithelial cells to secrete GM-CSF in vitro; (b) demonstrate differences between normal and inflamed tissue-derived epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1991

Neutrophilic differentiation induced by human upper airway fibroblast-derived granulocyte/macrophage colony-stimulating factor (GM-CSF).

We have established primary lines of fibroblasts from nasal polyp (NP) tissues as well as from normal nasal (NN) mucosa and have examined the ability of these cells to release hormone-like peptide messenger molecules (cytokines). Our results show that human upper airway fibroblasts release granulocyte/macrophage colony-stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), and macrophage-CSF (M-CSF) in vitro. We also show that fibroblasts derived from NP tissue express the gene for GM-CSF at a higher level, and release the GM-CSF product in greater amounts, than NN fibroblasts. In addition, we have examined the ability of these fibroblasts and their conditioned medium (CM) to induce differentiation of human hemopoietic progenitor cells. After 7 d, cultures of these cells in RPMI-10% fetal bovine serum contained 5 +/- 2.5% (mean +/- SD) neutrophils. In contrast, culture of progenitor cells with fibroblasts resulted in significantly greater neutrophilic differentiation (18 +/- 4%). Culture in fibroblast-CM induced a similar degree of differentiation, and fibroblast-CM from NP fibroblasts elicited greater differentiation compared to CM from NN fibroblasts (17.5 +/- 3 versus 12 +/- 3%). The neutrophilic differentiation induced by fibroblast-CM can be fully inhibited by preincubating this CM with a monoclonal neutralizing antibody to human GM-CSF. Thus, our results demonstrate: (1) the ability of human upper airway fibroblasts to release GM-, G-, and M-CSF in vitro; (2) that fibroblasts derived from NP tissues express the gene and release the product GM-CSF at greater levels compared to NN fibroblasts; and (3) that fibroblast-derived GM-CSF causes neutrophilic differentiation of human hemopoietic progenitors.

Animals↗
PubMed1991

Monocyte-macrophage differentiation induced by human upper airway epithelial cells.

We examined the ability of conditioned medium (CM) generated by human upper airway epithelial (Ep) cells from normal (NN) and inflamed, allergic rhinitis (AR) and nasal polyp (NP) tissues to induce monocytic differentiation of hemopoietic progenitors of the HL-60 myeloid leukemia cell line in vitro. In HL-60 cells cultured in RPMI with 10% FBS, there was differentiation to 0.4 +/- 0.4% monocytic cells. NN-, AR-, and NP-EpCM induced differentiation to 23 +/- 6%, 42 +/- 11%, and 71 +/- 10% monocytic cells, respectively. EpCM also induced isolated peripheral blood nonadherent mononuclear cells to express monocyte/macrophage-specific antigens as detected by immunohistochemistry using FMC-32 monoclonal antibodies (anti-CD14). We also examined the cytokine content of these EpCMs and found that they contained granulocyte/macrophage colony-stimulating factor (GM-CSF): 126 +/- 35, 198 +/- 22, and 489 +/- 118 pg/ml for NN-, AR-, and NP-EpCM, respectively. These CMs also contained granulocyte-CSF (G-CSF) and interleukin-6 (IL-6), but there were no significant differences between normal and inflamed tissue-derived cell supernatants. No macrophage-CSF (M-CSF) was detected in these EpCMs. Recombinant human GM-CSF, G-CSF, and IL-6, alone and in combinations, at doses similar to or greater than those found in the EpCMs, did not induce comparable monocytic differentiation of HL-60 cells. Preincubation of the EpCM with neutralizing anti-GM-CSF, anti-G-CSF, or anti-IL-6 antibodies did not significantly inhibit the monocytic differentiation induced by the EpCM.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation↗
PubMed1991

Promotion of eosinophil survival by human bronchial epithelial cells and its modulation by steroids.

Accumulation of eosinophils in the bronchial tissue occurs in a variety of inflammatory disorders of the human airway. We asked whether airway epithelial cells released factors that could influence eosinophil survival and thus contribute to accumulation of these cells in the tissues. Using conditioned medium (CM) generated from cultured human bronchial epithelial cells (HBEC), we examined the in vitro survival of eosinophils isolated from human peripheral blood. When cultured in control medium, more than 90% of the eosinophils were dead by day 4. In contrast, culture in HBEC-CM resulted in dose-dependent survival at day 6 of 69 +/- 9.4%, 40.5 +/- 5.9%, and 25 +/- 2% viability with 2, 0.5, and 0.1% HBEC-CM, respectively (n = 4). Granulocyte/macrophage colony-stimulating factor (GM-CSF) was detected in the HBEC-CM by enzyme-linked immunosorbent assay at levels of 22 to 48 pg/ml. Furthermore, preincubation of the HBEC-CM with a neutralizing monoclonal antibody to human GM-CSF completely inhibited this increased survival of eosinophils. Because corticosteroids are potent eosinopenic agents, we also examined the effects of the synthetic steroid budesonide on this system. Budesonide inhibited both spontaneous and interleukin-1 (IL-1)-induced GM-CSF production by cultured HBEC. In addition, preincubation of eosinophils with budesonide caused marked abrogation of the survival induced subsequently with either HBEC-CM or recombinant human GM-CSF. In summary, HBEC can support eosinophil survival via the elaboration of GM-CSF and thus may contribute to the local control of inflammatory cell accumulation. Steroids may modulate this process both by inhibiting cytokine production from HBEC and by a direct effect on eosinophils, preventing their response to cytokines.

Antibodies↗
PubMed1986

IgE antibody-mediated shock reaction caused by topical application of chlorhexidine.

A case of an anaphylactic shock following topical application of chlorhexidine preparation is reported. Specific skin-sensitizing antibodies against chlorhexidine were demonstrated in the serum from the patient by a passive transfer test. IgE antibodies against chlorhexidine were also detected by radioallergosorbent technique (RAST). Paper discs conjugated with chlorhexidine-HSA (human serum albumin) significantly bound the IgE antibodies. Furthermore, all of the sera from seven other patients with shock reactions following the topical application of chlorhexidine preparation also showed high RAST counts. Both chlorhexidine gluconate and chlorguanide which represents approximately half a molecule of chlorhexidine inhibited the reaction in a dose-dependent fashion. It is suggested that the shock reactions following topical application of chlorhexidine are mediated by IgE antibodies against chlorhexidine and that chlorhexidine and chlorguanide share the same antigenic determinant.

Administration, Topical↗