Mechanism of development of nasal hyperreactivity

1)鼻粘膜肿胀是由海绵窦扩张和血浆渗出引起的。轴突反射、神经节反射和副交感反射仅部分参与抗原攻击后早期观察到的鼻黏膜肿胀。参与血管平滑肌扩张最深入的神经递质是副交感神经末梢释放的NO。然而，在抗原攻击后的后期观察到的鼻黏膜肿胀的主要部分是由化学介质对血管平滑肌的直接作用引起的，其中最重要的是多肽白三烯(LTS)2)各种介质包括LTS、组胺和缓激肽通过作用于内皮细胞而引起血管平滑肌的扩张，从而释放NON。鼻部高反应性的机制1)非花粉S…期间反复抗原攻击的机制Eason浓度越高，鼻腔对组胺的高反应性越强。单一抗原攻击可引起鼻腔灌洗液中各种炎性细胞的显著增加，尤其是EG2阳性、活化的嗜酸性粒细胞，并伴随ECP.抗原攻击引起鼻黏膜IL-5m RNA和IL-5的显著增加。IL-5可增加鼻变态反应者鼻粘膜ICAM-1m RNA和鼻腔灌洗液中ICAM-1的表达。2)刺激培养的人鼻上皮细胞和内毒素可显著产生RANTES，鼻变态反应患者鼻黏膜上皮细胞RANTES的产生显著增加。4)预先给予抗VLA4单抗可抑制嗜酸性粒细胞与内皮细胞的黏附。4)预先给予抗VLA4单抗可抑制豚鼠鼻变态反应模型中嗜酸粒细胞的浸润和LTS的产生。5)鼻变态反应豚鼠上皮细胞H1受体m RNA的表达明显增强。雌激素和孕激素刺激培养的人鼻上皮细胞可显著增加H1受体m RNA的表达。较少

I Mechanism of development of hyperreactive nasal symptoms in nasal allergy.1) Nasal mucosal swelling is caused by dilatation of the cavernous sinces and plasma extravasation. Axon reflex, ganglion reflex and parasympathetic reflex participate only partially in development of nasal mucosal swelling observed in early phase after antigen challenge. The neurotransmitter which is most deeply involved in dilatation of vascular smooth muscle is NO released from parasympathetic terminals. However major partion of nasal mucosal swelling observed particularly in later phase after antigen challenge is caused by direct effects of chemical mediators on the vascular smooth muscle, the most important of which is peptide leukotriene (LTs).2) Various mediators including LTs, histamine and bradykinin cause dilatation of vascular smooth muscle by acting on endothelial cells which release NO.II Mechanism of nasal hyperreactivity1) Repeated antigen challenge in subjects with pollinosis during non-pollen s … More eason caused significant increase of nasal hyperreactivity to histamine. Single antigen challenge caused significant increase of various inflammatory cells, particularly EG2 positive, activated eosinophils in the nasal lavages with concomitant increase of ECP.Antigen challenge caused significant increase of IL-5 m RNA and IL-5 in the nasal mucosa in subjects with nasal allertgy. IL-5 increased ICAM-1 m RNA in the nasal mucosa and solble ICAM-1 in nasal lavages in subjects with nasal allergy.2) Stimulation of cultured human nasal epithelial cells and endothel caused significant production of RANTES, RANTES production was significantly enhanced in epithelial cells obtained from nasal allergy patients.3) Stimulation of cultured human endothel by histamine in concentration above 10^<-5> M caused significant increase of eosinophil adhesion to endothelium, which was inhibitted signifiantly by premedication of anti ELAM 1 antibody.4) Premedication of anti VLA 4 monoclonal antibody inhibitted eosinophial infiltration and LTs production observed on antigen challenge in guinea pig model of nasal allergy.5) Expression of H1 receptor m RNA in epithelial cells was significantly enhanced in subjects with nasal allergy. Stimulation of cultured human nasal epithelial cells with beta estrogen and progesteron increased H1 recepter m RNA expression significantly. Less