A STUDY ON MECHANISM OF THE DELAYED CELL IMPAIREMANT OF THE AIRWAY MUCOSA - RELEVANCE OF THE LIPID MEDIATORS TO NITRIC OXIDE AND SUPER OXIDE -

本课题旨在阐明鼻变态反应患者的鼻黏膜损害，为解决脂质介质诱导气道黏膜迟发性损害的机制提供线索。在鼻过敏患者的鼻灌洗液中测定了以下物质，并测定了血清和灌洗液中的尿素，以便在鼻分泌物中转化。结果：以下表现为显著相关；1)碱性磷酸酶活性（ALP）和LDH活性（LDH）， 2) ECP和LDH， 3) ECP和ALP， 4) NO和硝基酪氨酸（NT）， 5) NT和ALP，尽管以下各项无显著关系，6)NT和LDH， 7) ECP和NT。这些提示：(1)过敏性鼻黏膜损伤，(2)鼻黏膜细胞膜损伤和胞浆中LDH的通量，(3)NO和超氧化物系统对细胞膜的损伤。(4)细胞膜ALP通量与细胞质ADH通量的显著差异；(5)NO和超氧化物蛋白损伤系统独立于嗜酸性粒细胞颗粒蛋白损伤系统。将术中获得的10^<-7> M、10^<-8> MLTD_4或PAF暴露于鼻黏膜前后，测定培养基中的LDH、ALP、NO和NT。结果：这些物质在发育过程中有增加的趋势。(2)白三烯受体拮抗剂pranlukast在培养基中抑制LTD_4诱导的这种增加。(3)与对照组相比，暴露于脂质介质的鼻黏膜被抗nt抗体弥漫性染色。(4)暴露于LTD_4或PAF 24小时后，在人支气管上皮细胞培养液中检测到NT。这些数据提示鼻灌洗液中检测到的NT可能不仅来自上皮细胞，也来自其他粘膜成分细胞。为了进一步研究脂质介质诱导迟发性粘膜细胞损伤的机制，需要进一步研究黄嘌呤氧化酶和一氧化氮合酶的mRNA水平。

The aim of this project is to clarify nasal mucosal impairment in nasal allergy patients and to get clues to the solution of the mechanisms of lipids mediators induced delayed impairment of airway mucosa.I. The following substances were measured in the nasal lavage fluids from nasal allergy patients, and urea was also measured in sera and the lavage fluids for conversion in the nasal secretions. Results : Followings showed significant relationships ; 1) alkariphosphatase activity (ALP) and LDH activity (LDH), 2) ECP and LDH, 3) ECP and ALP, 4) NO and nitrotyrosine (NT), 5) NT and ALP, although followings did not show significant relationships, 6) NT and LDH, 7) ECP and NT. These suggested (1) impairment of allergic nasal mucosa, (2) nasal mucosal cell membrane impairment and flux of LDH from cytoplasm, (3) cell membrane impairment by NO and superoxide system, (4) capable difference between fluxes of ALP from cell membrane and ADH from cytoplasm, (5) NO and superoxide protein impairment system is independent from eosinophil granule protein injurious system.II. LDH, ALP, NO and NT were measured in the medium before and after exposure of 10^<-7> M, 10^<-8> MLTD_4 or PAF to nasal mucosa obtained at a time of surgery. Results : These substances showed tend to increase in progress. (2) Leukotriene receptor antagonist, pranlukast, inhibited LTD_4 induced these increases in the medium. (3) The nasal mucosa exposed to lipid mediators were diffusely stained by anti-NT antibody compared to the control. (4) NT was detected in the culture medium with human bronchial epithelial cells following exposure to LTD_4 or PAF after 24 hours. These data suggest that NT detected in the nasal lavage fluids may be attributable from not only epithelial cells but also other mucosal component cells. For the further investigation of the mechanism of the lipid mediator induced delayed mucosal cell impairment, mRNA level of xanthine oxidase and nitric oxside synthase should be studied.