Nanako Hamano

Effect of sex hormones on eosinophilic inflammation in nasal mucosa.

We examined the effects of sex hormones on the functions of eosinophils. Treatment of eosinophils with beta-estradiol significantly enhanced the eosinophil adhesion to human mucosal microvascular endothelial cells (HMMEC), and eosinophils stimulated by a combination of beta-estradiol and progesterone showed significant induced degranulation. On the other hand, testosterone significantly reduced the eosinophil adhesion to HMMEC and eosinophil viability. The experiments from the series of studies might provide a partial explanation for the aggravation of asthma and some forms of rhinitis that occurs during pregnancy.

Expression of Histamine Receptors in Nasal Epithelial Cells and Endothelial Cells – The Effects of Sex Hormones

Background: Hyperreactivity of the nasal mucosa is a characteristic of nasal allergy. During pregnancy, aggravation of nasal allergic symptoms is occasionally observed in subjects with nasal allergy. Methods: Using the reverse transcription-polymerase chain reaction and Southern blot hybridization method, we investigated histamine H1 receptor mRNA (H1R mRNA) expressions in specimens of nasal epithelial layer obtained by scraping, as well as cultured human nasal epithelial cells (HNECs) and human mucosal microvascular endothelial cells (HMMECs). We compared the expressions on the specimens from patients with nasal allergy with those with nonallergic rhinitis or those from normal volunteers. In addition, we investigated the effects of female hormones on the H1R mRNA expressions in HNECs and HMMECs. Results: H1R mRNA was detected in scraped specimens of nasal epithelial layer, as well as in HNECs and HMMECs. The mRNA expressions in nasal mucosal scraped specimens of epithelial layers and HNECs were more marked in patients with nasal allergy than in the other two groups. In addition, the present study demonstrates that the female hormones β-estradiol and progesterone significantly increase the expressions of H1R mRNA on HNECs and HMMECs. Conclusion: The increase of the expressions of H1R mRNA may explain, in part, the nasal hyperreactivity to histamine observed in patients with nasal allergy. It has also been suggested that sex hormones are related to the preponderance of females in the incidence of allergic rhinitis after puberty, and that they are related, at least partially, to the aggravation of the nasal hyperreactivity symptoms during pregnancy through the enhanced expression of H1R mRNA on HNECs and HMMECs.

Diesel exhaust particulates enhance eosinophil adhesion to nasal epithelial cells and cause degranulation

Diesel exhaust particulates (DEP) are a common air pollutant from diesel-engine-powered car exhaust and are thought to cause chronic airway diseases. On the other hand, eosinophils are major components of allergic inflammatory disorders such as asthma, nasal allergy and atopic dermatitis. We examined the effects of DEP and DEP extract (extract of polyaromatic hydrocarbons) on eosinophil adhesion, survival rate and degranulation. Eosinophils, human mucosal microvascular endothelial cells (HMMECs) and human nasal epithelial cells (HNECs) were preincubated in the presence or absence of DEP and DEP extract. 35S-labeled eosinophils were allowed to adhere to monolayers of HMMECs and HNECs. After washing, 35S radioactivity was determined and numbers of adherent eosinophils were calculated using each standard curve. The effects of DEP and DEP extract on eosinophil survival rate and degranulation were also determined. Although neither DEP nor DEP extract affected the adhesiveness of HMMECs and HNECs to eosinophils, 5 ng/ml of DEP extract and 50 ng/ml of DEP extract each significancy increased eosinophil adhesiveness to HNECs (134+/-9 and 143+/-8%, respectively; p<0.01 vs. control), but neither effected eosinophil adhesiveness to HMMECs. DEP extract also induced eosinophil degranulation without changing the eosinophil survival rate. Given that eosinophil-derived lipid mediators and toxic proteins play important roles in the development of nasal allergy, the above findings strongly suggest that DEP plays an important role in promoting the nasal hypersensitivity induced by enhanced eosinophil infiltration of epithelium and eosinophil degranulation.

Effect of Female Hormones on the Production of IL-4 and IL-13 from Peripheral Blood Mononuclear Cells

In this study we compared the concentrations of IL-4, IL-13, and IFN-gamma, which were produced by human peripheral blood mononuclear cells (PBMC) in the presence or absence of preincubation with beta-estradiol or progesterone both after a specific antigen challenge and without a specific antigen challenge. The concentrations of IL-4 and IL-13 from PBMC which had been preincubated with progesterone or gamma-estradiol for 18-24 h were significantly greater than those of IL-4 and IL-13 from PBMC which had been preincubated with PBS, the control. On the other hand, the concentration of IFN-gamma from PBMC was unchanged. We were able to confirm that the female hormones beta-estradiol and progesterone, at levels similar to those occurring during pregnancy, have the ability to induce production of IL-4 and IL-13 in human mononuclear cells. These results suggest that female hormones may aggravate nasal allergy symptoms during pregnancy by increasing IgE synthesis and inducing selective eosinophil infiltration.

RANTES production in nasal epithelial cells and endothelial cells.

BACKGROUND It is well documented that the chemokine that is regulated upon activation, normal T expressed and presumably secreted, RANTES, is produced by macrophages, platelets, fibroblasts, and renal tubular epithelial cells. Recently, however, production of RANTES by vascular endothelium and airway epithelial cells was demonstrated in human umbilical vein endothelial cells (HUVECs) and epithelial cell lines. OBJECTIVE This investigation was aimed at determining whether human nasal epithelial cells (HNECs) and human mucosal microvascular endothelial cells (HMMECs) produce RANTES when they are stimulated by several cytokines. METHODS HNECs and HMMECs were isolated from nasal mucosa and subsequent continuous subcultures and were stimulated either by IL-1 beta or by the combination of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). RESULTS After the combined stimulation by TNF-alpha and IFN-gamma, HNECs and HMMECs dramatically produced RANTES, as previously observed in HUVECs and bronchial epithelial cell line BEAS-2B. IL-1 beta also increased RANTES production to a lesser extent. We also demonstrated that the amount of RANTES induced by TNF-alpha and IFN-gamma was higher in HNECs and HMMECs obtained from patients with nasal allergy than in those from patients without allergy. CONCLUSION RANTES from HNECs and HMMECs likely plays a critical role in eosinophil infiltration of the nasal mucosa in subjects with nasal allergy.

The potential role of interleukin-13 in eosinophilic inflammation in nasal mucosa.

Background Recent studies have revealed that interleukin (IL)‐13, as well as IL‐4, causes de novo surface expression of vascular cell adhesion molecule‐1 (VCAM‐1) on endothelial cells of the umbilical vein and accelerates selective eosinophil migration. However, its role in allergic rhinitis remains to be clarified. Of particular interest is whether IL‐13 upregulates VCAM‐1 expression in human mucosal microvascular endothelial cells (HMMECs), to which eosinophils adhere in nasal mucosa.

Late Phase Response in Nasal Mucosa Closely Correlated with Immediate Phase Reaction and Hyperreactivity to Histamine

It has been suggested that the onset of the late phase response (LPR) and hyperreactivity to non-specific stimuli occurs in the lower airway. However, its relationship in the nose has not yet been studied. This study was designed to examine the mechanism of LPR and the relationship between LPR and hyperreactivity. A total of 25 Japanese cedar pollinosis patients participated in this study. On the first visit, the frequency of sneezes, weight of nasal discharge, and the nasal airway resistance (NAR) were time-dependently measured without antigen challenge. The histamine reactivity was observed after 12 h. The same protocol was used during the second to fourth visits. The frequency of sneezes, weight of nasal discharge, and NAR were measured continuously for 12 h after antigen challenge, and nasal reactivity to histamine was observed. The percent change of NAR during immediate phase response (IR) and during LPR showed a significant correlation. The frequency of sneezes and weight of nasal discharge induced by histamine were both significantly higher in the positive than in the negative LPR group. These results suggest that the chemical mediators and inflammatory cells inducing nasal swelling during IR cause, directly or indirectly, nasal swelling during LPR, and induce hyperreactivity to histamine.

Changes in nasal responsiveness to histamine and to specific antigen after laser surgery.

An initial treatment with several kinds of anti-allergic medicines is useful for reducing nasal allergy symptoms in patients suffering from Japanese cedar pollinosis during the pollen season. Since laser surgery before the pollen season seems to have a preventive effect as well, it would be of interest to know the time course of changes in the nasal reactivity to specific and non-specific stimuli after laser surgery. In this study, we investigated the changes in the nasal reactivities to specific antigen and histamine after CO2 laser surgery. The nasal reactivities to both specific antigen and histamine were enhanced 2 weeks after the laser surgery. On the other hand, they were significantly reduced after 4 weeks. Our data strongly suggest. therefore. that laser surgery must be done more than 4 weeks before the start of the pollen season to avoid temporary enhancement of nasal allergy symptoms.