| INTRODUCTION: Airway allergic inflammation induced by eosinophilsand mast cells and bronchial hyperreactivity are characteristic features ofasthma. lnfiltration and activation of eosinophils is impoftant for asthm4pathogenesis. In airway inflammation of asthIna, many factors take part ineosinophils chemotaxis, infiltration and activation, and the release ofinflammatory mediator. Vascular cell adhesion molecule-l (VCAM-l) isconsidered to play a key role in eosinophil infiltration. ln asthma, epitheliummucosa was injured. Submucous sensory C-fibres is easily activated byinternal and extemal stimuli and release tachykinins, including subtance Pneurokinin A, neurokinin B. Tachykinins exeYt pro-inflammatory effects:inflammatory cell infiltration, microvascular leakage andbroncho-constriction etc. Tachykinin NK-1 receptors are involved invasodilatation, increasing plasma protein extravasation, chemotaxis andactivation of inflammatory cell etc. Recently, tachykinin NK-1 receptoraniagonists were shown to have aflti-inflammatory and ami-asthIna effectson experiment animals, but their effect on VCAM-l expression has not beeninvestigated.AIM: This study aims to determine the expression and pharmacologicalmodulation of VCAM-1 in the lungs of rats with allergic airwayinflammation, with emphasis on the possible effects of SR 140333, { (S ) -l- (2-[ 3, 4-dichlorophenyl ] --l-(3-isopropoxyphenylacetyl ) piperidin-3-yl ) ethyl-4-phenyl-l-azoniabicyclo [ 2. 2. 2 ] octane. chloride }, aselective NK-1 receptor antagonist, on VCAM-1 expression and eosinophilinfiltration.METHODS: Ovalbumin-sensitized rats were challenged with inhalation ofl% ovalbumin aerosol. SR140333 (0.0l and 0.l0 mg. kg-') anddexamethasone (0.50 mg. kg-') were injected intraPaitontally, twice a day,from dl3 to d15 after sensitization. Twenty four hours after challenge,protein eXPression of VCAM-1 in the lungs was determined with westernblot; the lung sections were stained with hematoxylin-eosin and eosinophilinfiltration around bronchi was measured.RESULT: @VCAM-1 expression in rat lungs. Under our experimentalconditions, a constitutive expression of VCAM-l was present in lungs ofnon-sensitized rat after saline chal1enge (n = l0, 1.l2 i0.38). A laterchallenge of non-sensitized rats with ovalbumin did not change VCAM-lexpression (n = l0; 1 .l9l0.2l). The VCAM-l experssion was enhancedsignificantly in lungs of sensitized rat after saline challenge (n = l0; l .44 i0.30; P < 0.05) compared with that from non-sensitized rats (about a 29%increment). Later, ovalbumin challenge of sensitized rats did not furtherincrease the VCAM-l expression in the lungs (n = l0; l.43f0.22). @Effects of ovalbumin sensitization and ovalbumin challenge on eosinophilinfiltration in rats lungs. In non-sensitized rats lungs, only a few ofeosinophils were found around the bronchi regardless of challenge withsaline (n = l0, 0.02 i0.06) or ovalbumin (n = l0; 0i 0). In sensitized ratswith saline challenge, also found a few of eosinophils infiltrated aroundbronchi (n = l0; 0.30f0.68). Challenge of sensitized rats with ovalbuminsignificantly enhanced eosinophil infiltration around the bronchi (n = l0;2.64 l 0.68; P < 0.05), comPared with that from non-sensitized ratschallenged with saline. @' Effects of dexamethasone and SRl40333 onVCAM-1 expression and eosinophil infiltration in lungs of sensitized rats.In the lungs of sensitized rat after saline challenge, the enhanced VCAM-lexpression was inhibited (n = 10; l .l0l0.31; P < 0.05) by pretreatmentwith dexamethasone (0.50 mg. kg-', ip), but dexamethasone did not changethe eosinophil infiltration compared with that from control. In the sensitizedrats with saline challenge pretreatmented with SRl40333 (0.01 and 0.10mg. kg-', ip), VCAM-l expression and eosinophil infiltration in lungs hadno change. @ Effects of dexamethasone and SRl40333 on VCAM-lexpression and eosinophil infiltration... |
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