Homes are being built to be more airtight because of demands for energy conservation in recent years. At the same time, recognition of numerous sources of formaldehyde in indoor environments has increased concerns about health hazards from this pollutant. Formaldehyde has been shown to cause and exacerbate asthmatic symptoms. In addition, the effects of formaldehyde on the airway are proportional to the concentration and duration of exposure and are greater in inflamed than in healthy airways. Formaldehyde may induce features of airway inflammation associated with asthma, such as epithelial disruption, microvascular leakage and increased airway secretions. Exposure to this chemical may facilitate IgE sensitization to a variety of allergens, as well as producing IgE-mediated allergic responses to itself. Thus, avoidance of formaldehyde exposure may reduce the incidence and severity of asthma, although the ability of low concentrations of formaldehyde to trigger mechanisms contributing to asthmatic symptoms is still debated. Setting appropriate exposure limits for formaldehyde as an indoor environmental pollutant requires further quantitative and predictive evaluation of its health effects.

View full abstract

We are analysing the initial molecular events stimulated by the high-affinity receptor for IgE, FcεRI. Earlier studies have shown that the first response when the receptor-bound IgE interacts with a multivalent antigen is a transphosphorylation of receptor tyrosines, induced by the approximation of two or more receptors by a constitutively associated src-family kinase (Lyn). The amount of weakly associated kinase regulates the intensity of the response. Several aspects are being analyzed: (i) the sites on Lyn and the receptor that account for the constitutive interaction; (ii) how the intrinsic affinity of a ligand for the receptor-bound IgE influences the responses; and (iii) the mechanism(s) by which low-affinity ligands can act as antagonists. In the latter studies, mast cell responses were followed by monitoring the phosphorylation of tyrosines on several proteins and secretion. At equivalent levels of receptor phosphorylation, a ligand with high affinity stimulated vigorous phosphorylation of downstream components, whereas a low-affinity ligand was unable to stimulate phosphorylation of the same components effectively. Cells stimulated with a mixture of high- and low-affinity ligands, under a protocol where simple displacement of one by the other was prevented, remarkably showed that excess low-affinity ligand inhibited the phosphorylation as well as degranulation by the high-affinity ligand. This antagonism results from a competition for the limiting amount of the constitutive initiating kinase. Related receptors that depend on recruitment of initiating kinases may be subject to similar regulatory mechanisms.

View full abstract

Allergic diseases, such as atopic rhinitis, bronchial asthma and urticaria, are prevalent and increasing in frequency. Mast cells are known to play a central role in the immediate phase reaction of allergic diseases through the IgE-mediated release of a variety of chemical mediators, such as histamine, leukotrienes and prostaglandins. In contrast, T lymphocytes, basophils and eosinophils are thought to be responsible for inducing the late phase response. However, whether the mast cell can be simplistically assigned a role in the immediate phase allergic response and whether mast cells are necessary for the ongoing allergic response, including the development of hyperresponsiveness, remains to be completely studied. In the present article, the author will discuss the integrated roles of mast cells in IgE-mediated allergic inflammation, with specific emphasis on the roles of mast cell-derived cytokines in the late phase allergic response and chronic allergic inflammation.

View full abstract

We evaluated high-affinity receptor for IgE (FcεRI)-binding serum IgE in patients with atopic kerato- conjunctivitis (AKC; n = 31) and with seasonal allergic conjunctivitis (SAC; n = 13) by enzyme-linked immunosorbent assay (ELISA) using a recombinant soluble form of the human FcεRIα ectodomain (soluble α). The quantities of FcεRI-binding IgE are compared with those of total IgE measured by a conventional sandwich ELISA. Both of the quantities of FcεRI-binding and total IgE in AKC were significantly larger than those in SAC (P < 0.001). In contrast, the proportion of FcεRI-binding IgE (FcεRI-binding IgE/total IgE; %) in SAC was significantly larger than that in AKC (P < 0.001), although significant reverse correlation was observed between the proportion of FcεRI-binding IgE and total IgE in both AKC and SAC. Significantly, a higher proportion of FcRI-binding IgE in SAC than that in AKC may reflect the differences in pathologic states of AKC and SAC that are caused by a disparity in immune responses in these diseases.

View full abstract

The immunosuppressive effect of ethyl O-(N-(p- carboxyphenyl)-carbamoyl)-mycophenolate (CAM) was examined in interphotoreceptor retinoid-binding protein (IRBP)-induced experimental autoimmune uveoretinitis (EAU) in rats. Lewis rats immunized with bovine IRBP were treated with various oral doses of CAM postimmunization. The degree of inflammation was assessed clinically each day and histologically on day 14 or day 20. Production of various cytokines and IRBP-specific antibody, as well as IRBP-specific proliferation response, was assessed. Complete inhibition of EAU in rats, both by clinical and histologic criteria, was achieved with 50 mg/kg CAM when administered daily for 14 days following IRBP immunization. Partial inhibition was observed at lesser doses of CAM. This CAM-mediated response was accompanied by diminished production of cytokines interleukin-2, interferon-γ and tumor necrosis factor-α, as well as a reduction in IRBP-specific antibody production. Furthermore, administration of CAM either in the induction phase only (days 0-7) or in the effector phase only (days 9 or 11 to day 20) was also capable of suppressing EAU, as assessed histopathologically on day 20. We conclude that CAM is effective in suppressing EAU in rats and its mechanism of action appears to involve modulation of T cell function.

View full abstract

A new method is described for the quantitative detection of IgE antibodies, based on IgE capture with a specific antibody, reaction with liquid-biotinylated allergens and biotinylated anti-IgE and immunoenzymatic development of the reaction (reverse enzyme allergosorbent test). Using a reference system based on the World Health Organization IgE International standard, this method determines total IgE in the range 2-100 kU/L and specific IgE in the range 0.2-100 kU/L, from which the specific/total ratio, called 'specific IgE density', can be calculated. This procedure has been applied to the study of specific IgE in 23 sera from patients polysensitized to pollen and mite allergens: 11 with asthma and 12 with rhinitis. The sensitivity and reproducibility of the method were evaluted. Sera from asthmatic patients showed higher cumulative levels of specific IgE (mean density 57.7%) than sera from rhinitic patients (mean density 32.6%). The clinical significance of specific IgE density in patients with multiple sensitizations is discussed.

View full abstract

Although various types of stress activate a pituitary adrenal response, the alteration of endogenous corticosteroids and catecholamines during asthma remains unclear. The aim of this study was to assess changes in endogenous corticosteroid and catecholamine levels in allergic eosinophilic inflammation in rats, using metabolic cages. Brown Norway rats (female, 6 weeks old) were sensitized with intraperitoneal injections of ovalbumin on days 0 and 2 and challenged with either an aerosol of ovalbumin or saline for 30 min on day 21. Levels of urinary 11-hydroxycorticosteroid (OHCS), a primary metabolite of corticosterone; epinephrine and norepinephrine were determined in pooled samples taken 0-24 h before and 8-32 h after the challenge. Serum adrenocorticotropic hormone, corticosterone levels and cell counts in bronchoalveolar lavage fluid were assessed 32-36 h after the challenge, as well as lung eosinophil peroxidase activity, an indirect index of eosinophil infiltration. The numbers of total cells and eosinophils in bronchoalveolar lavage fluid and lung eosinophil peroxidase activity were significantly increased in the ovalbumin-challenged rats compared with the saline-challenged rats. While urinary OHCS and serum corticosterone levels were significantly increased after challenge in the ovalbumin-challenged rats, compared with the saline-challenged rats (2.1 ± 0.1 × 10^-1vs 1.7 ± 0.1 × 10^-1 mg/g creatinine, P < 0.05 and 482 ± 49 vs 348 ± 19 ng/mL, P < 0.02, respectively), serum adrenocorticotropic hormone levels did not differ between the two groups. Urinary epinephrine and norepinephrine excretion also did not differ between the two groups. It is concluded that endogenous corticosterone, but not catecholamine, increases as a pathophysiologic adrenal response, possibly to protect lung during allergic eosinophilic inflammation.

View full abstract

The presence of IgE antibodies to the allergens rBetv1 and rBetv2 was investigated in the sera of 99 patients with specific IgE to apple extract by comparing a group of 43 patients who had oral allergy syndrome (OAS) after ingestion of apple with a group of 56 patients without OAS who had only seasonal respiratory symptoms. The incidence of the presence of IgE antibodies to rBetv1 was 88.1%. All patients had levels of IgE to apple extract greater than 0.35 kU/L. After eating apple, patients allergic to birch pollen with OAS showed significantly higher levels of IgE to apple extract and rBetv1 than patients without OAS (P = 0.007 and P = 0.0002, respectively). Twenty of 56 patients (35.7%) in the group without OAS who produced specific IgE to apple did not have specific IgE against rBetv1 and rBetv2 and were symptomless after eating apple. In conclusion, patients allergic to birch pollen with specific IgE to rBetv1 showed a significantly elevated frequency of apple allergy. In contrast, our results show that fruit-related symptoms require not only high specific serum IgE levels, but a strong cellular sensitization to birch pollen allergens, together with an increased cellular reactivity to apple allergens.

View full abstract