Lipid bodies are non-membrane bound, lipid-rich cytoplasmic inclusions that form in diverse cell types. Characteristically, lipid body numbers increase when eosinophils and other leukocytes are participating in inflammatory processes. Moreover, lipid bodies are numerous in other sites active in eicosanoid formation, such as the amnion epithelium at parturition. Our interests in lipid bodies relate to the roles that these structures play in arachidonate metabolism by eosinophils and other leukocytes involved in inflammation. Findings indicate that lipid bodies in these leukocytes can function as intracellular domains that are both depots of esterified arachidonate and sites at which regulated enzymatic events relevant to arachidonate metabolism can occur. Lipid bodies are discrete intracellular structures whose formation is specifically inducible early, whose increased numbers correlate with the ‘priming’ responses of leukocytes to form enhanced amounts of both cyclooxygenase- and lipoxygenase-derived eicosanoids and whose inhibition of formation correlates with reduced synthesis of these eicosanoids. Inhibition of lipid body formation represents a novel pharmacologic target to block the formation of eicosanoid mediators of inflammation.
The serum levels of soluble CD23 (sCD23) were examined in patients with multiple myelomas and related diseases and were compared with levels of sCD23 in healthy, age- and sex-matched controls. The mean levels (95% confidence intervals) of sCD23 in the sera of 40 patients with multiple myelomas, nine patients with myeloma-related diseases (seven primary macroglobulinemia and two chronic lymphatic leukemia) and 30 matched controls were 2.7 (1.9-3.8), 9.9 (5.1-19.2) and 1.5 (1.3-1.7) ng/mL, respectively, showing a significant increase in sCD23 in the circulation of patients with myelomas (P<0.01) and myeloma-related diseases (P<0.001). The potential biologic importance of sCD23 in myelomas and related diseases is discussed.
The requirement of RNA polymerase proteins and transcription factor proteins for the expression of genetic information in DNA clearly indicates that the process is influenced by certain proteins in the body and/or in the environment, which is totally opposite to the ‘central dogma’ of Crick. In this article, we present a working hypothesis (helical hypothesis) that may explain the programmed nature of various biological events simply and naturally. Future investigations on the factors that regulate the gene transcription of cytokine clusters, including intereukin (IL)-4 and IL-5, may provide an answer for controlling atopic as well as other hereditary (genetic) diseases.
Aspirin-induced asthma is often accompanied by nasal polyps, in which tissue eosinophils are abundant and activated. However, the mechanism of eosinophil infiltration remains unknown. We encountered two aspirin-induced asthma patients with nasal polyps and investigated eosinophil infiltration into nasal polyp tissue. Eosinophil chemotactic activity of extracts from the nasal polyp was elevated and could be inhibited by 40% with anti-interleukin (IL)-5 antibody. Interleukin-5 was detectable in the extract. The chemotactic activity of peripheral blood eosinophils to recombinant human (rh)IL-5 was increased compared with normal volunteers. Messenger RNA expression for IL-5 in CD3+ lymphocytes for polyp tissue was detected using the reverse transcription-polymerase chain reaction. These results suggest that IL-5 from local T lymphocytes may be one of the candidates for recruitment of eosinophils into nasal polyps in aspirin-induced asthma.
In the United States and Europe, gastroesophageal reflux (GER) is receiving attention as a potential cause of bronchial asthma. Few Japanese case reports have described this relationship. Therefore, we investigated the effect of omeprazole and cisapride on pulmonary function tests, blood gases and home peak expiratory flow rates (PEFR) in six Japanese outpatients with asthma and proven GER. After 8 weeks of treatment, reflux esophagitis had improved in all patients. However, the parameters of pulmonary function showed no change other than a significant post-treatment increase in home PEFR (4.4-27.7%) in three patients. These results suggest that anti-reflux (omeprazole and cisapride) treatment will produce small improvements in the PEFR in some Japanese asthmatics with GER.
To estimate the levels of serum IgE that is actually able to be bound to Fc∈Rl, we developed a novel enzyme-linked immunosorbent assay (ELISA) using a recombinant soluble form of the human Fc∈Rlα ectodomain (soluble α-ELISA). We evaluated the levels of Fc∈Rl-bindable serum IgE in normal volunteers and in patients with atopic dermatitis and bronchial asthma, and compared them with those of total IgE measured by a conventional sandwich-ELISA. There was a striking difference between the IgE values evaluated with these two ELISA systems. In most of the sera, the IgE values evaluated with the soluble α-ELISA were substantially lower than those evaluated with the sandwich-ELISA. Our results indicate that all serum IgE (especially in hyper-IgE sera) does not necessarily bind to the Fc∈Rl and that it will be useful to evaluate Fc∈Rl-bindable IgE for further analysis of allergic states.
N-3 fatty acids, such as fish oil, have been reported to have some beneficial effects in patients with bronchial asthma. The effects of dietary supplementation with perilla seed oil rich in α-linolenic acid (α-LNA), parent n-3 fatty acid, were studied in five patients with asthma. The symptoms of asthma and mean peak flow rates (PFR) both early in the morning and in the evening were improved 2 weeks after dietary supplementation and the increases in PFR were significant (P<0.05). The generation of leukotriene B4 (LTB4) by peripheral leukocytes stimulated with the Ca2+ ionophore A23187 was significantly suppressed from 77.6 to 41.6ng/5×106 cells by dietary supplementation (P<0.05). The generation of leukotriene C4 (LTC4) by leukocytes was also significantly suppressed from 64.0 to 38.8ng/5×106 cells after supplementation with perilla seed oil (P<0.05). These results suggest that dietary supplementation with perilla seed oil is beneficial for the treatment of asthma.
To determine anti-allergic effects of Koboku, a Chinese herbal medicine, we investigated its inhibitory action on the production of cysteinyl leukotrienes (LT) and LTB4, which are important chemical mediators in the pathogenesis of allergic diseases. A23187-stimulated synthesis of cysteinyl LT and LTB4 was measured by HPLC in the absence or presence of various concentrations of Koboku in rat basophilic leukemia-1 (RBL-1) cells. In a dose-dependent manner, Koboku inhibited synthesis of cysteinyl LT and LTB4 by up to 92.3 and 100%, respectively. Immunoglobulin E-mediated release of cysteinyl LT and LTB4, which was measured by specific radioimmunoassay (RIA) was also inhibited by Koboku in RBL-2H3 cells. Sites of inhibition of Koboku in the metabolic pathway of LT synthesis were phospholipase A2 (PLA2) and 5-lipoxygenase (5-LO), but not LTC4 synthase or LTA4 hydrolase. We conclude that the anti-allergic effect of Koboku may be attributable, at least in part, to the inhibition of LT synthesis.
We tried to evaluate the role of IgG antibodies in the wheal and flare reaction of infantile atopic dermatitis by in vivo skin-sensitizing methods. Sera from 49 patients under 6 years of age were heated at 56°C for 30min to inactivate IgE antibodies, according to previous reports. Two-fold serial dilutions of the heated serum were injected intracutaneously in both forearms of a non-allergic recipient. One hour later, the whole egg antigen (1:1000) was injected in the serum transfer sites of an arm and the reaction was read at 15min (IgG Prausnitz-Küstner (P-K) test). Immediately afterwards, a raw hen's egg was swallowed by the recipient and the serum transfer sites of the other arm were observed for 2h (oral IgG P-K test). Three patients under 1 year of age showed an immediate wheal and flare reaction in the IgG P-K test, but none of the patients showed a positive reaction in the oral IgG P-K test. The patients with a positive IgG P-K test had an IgE radioallergosorbent test (PAST) score >4 to egg white and a positive IgE P-K titer of >28 to whole egg antigen. Two patients showed a positive reaction to the oral IgE P-K test to raw egg ingestion. Ovalbumin-specific IgG1, IgG3 and IgG4 antibodies were assayed in 20 patients. IgG1 and IgG3 antibodies were significantly increased in two patients with a positive IgG P-K test, while levels of the IgG4 antibody in positive patients were not significantly increased in comparison with levels in negative patients. In conclusion, these results suggest that the IgG antibody may play a role in the immediate type allergic reaction in infantile atopic dermatitis.
Mercury sensitization has been historically in question and may be related to recent increases of type I allergic diseases. To clarify the epidemiological factors of mercury sensitization, we investigated factors relating to mercury sensitization in 215 medical students. Their allergic symptoms, family histories and lifestyles were studied by questionnaire. Patch tests were performed with HgCl2 (0.05% aq.) and NiSO4 (5% aq.). Anti-Dermatophagoides and anti-Cryptomeria pollen IgE antibodies in sera were also measured. Urinary mercury concentrations were measured in 25 mercury sensitized and 44 non-sensitized subjects (controls). Hair mercury concentrations were also measured in 19 sensitized and 22 non-sensitized subjects. While the positive rate of nickel was 6.0% (13/215), that of mercury was high (13.0%; 28/215). The subjects' individual histories of allergic rhinitis, eczema, urticaria and allergic conjunctivitis were significantly associated with family histories of these conditions (P<0.01, P<0.005 and P<0.005, respectively), as reported in the literature. However, no allergen-specific antibody positivity or past history of allergic disease was associated with mercury sensitization. Mercury sensitized subjects had experienced eczema caused by cosmetics, shampoos, soaps and haircreams significantly more frequently (P<0.05). The history of mercurochrome usage was not associated with mercury sensitization. The number of teeth treated with metals in mercury sensitized subjects was significantly higher than that in the control group (6.8±4.3 vs 4.8±1; P<0.05). There were significant differences in urinary mercury concentrations (specific gravity adjusted levels) between mercury sensitized subjects and non-sensitized subjects (2.0±0.9 and 1.3±0.6μg/L, respectively; P<0.001). There were also significant differences in hair mercury concentrations between mercury sensitized and non-sensitized subjects (2.0±0.9 and 1.2±0.5μg/g, respectively; P<0.01). These results suggest that mercury sensitization is associated with exposure to mercury in the living environment and that skin symptoms are possibly associated as preceding factors.
We developed a fluorometric enzyme-linked immunosorbent assay (ELISA) for allergen-specific IgE in dogs with the use of monoclonal anti-dog IgE; we assayed IgE antibody to Japanese cedar pollen in the sera of dogs with Japanese cedar pollinosis. To assess the specificity of this ELISA, a pooled serum sample from pollinosis dogs was subjected to gel chromatography. The peak of anti-pollen allergen IgE activity was different from the peaks of total IgA, IgG and IgM. When IgE antibody positive serum was heated at 56°C for 4h, antibody activity was markedly reduced. Furthermore, polyclonal anti-dog IgA, IgG and IgM did not interfere with anti-pollen allergen IgE activity in the ELISA. From these results, this assay is considered to have a high specificity for dog IgE.