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

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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.