Hojo M, Maghni K, Issekutz T B, Martin J G
Meakins-Christie Laboratories, McGill University, Montreal, Quebec; and the Izaak Walton Killam Children's Hospital, Grace Centre, Dalhousie University, Halifax, Nova Scotia, Canada.
Am J Respir Crit Care Med. 1998 Oct;158(4):1127-33. doi: 10.1164/ajrccm.158.4.9804001.
Antibodies against integrins have been shown to inhibit allergic airway responses. The purpose of this study was to test the hypothesis that the beta1 integrin, very late antigen-4 (VLA-4), is involved in mast cell activation triggered by allergen exposure in sensitized animals. To do this we studied Brown Norway rats that were sensitized to ovalbumin (OA; 1 mg subcutaneously) using Bordetella pertussis as an adjuvant. Two weeks later rats were challenged with OA, pulmonary resistance (RL) was determined, and the concentrations of histamine and tryptase in bronchoalveolar lavage fluid and N-acetyl-leukotriene (LT)E4 in bile were measured. Pretreatment with a monoclonal antibody against VLA-4 (TA-2) attenuated the early response after OA challenge (342.9 +/- 24.4% baseline RL versus 153.3 +/- 19.4%; p < 0.01). There were significantly lower concentrations of histamine (67.11 +/- 11.90 microgram/ml versus 26.69 +/- 1.84; p < 0.01) and tryptase (0.143 +/- 0. 035 microgram/ml versus 0.053 +/- 0.022 microgram/ml; p < 0.01) in TA-2-treated animals. The increases in the concentrations of biliary N-acetyl-LTE4 after OA challenge were also significantly lower in TA-2-treated animals. These data suggest that a selective anti-VLA-4 monoclonal antibody prevents early responses through inhibition of mast cell activation.
抗整合素抗体已被证明可抑制过敏性气道反应。本研究的目的是检验β1整合素，即极迟抗原-4（VLA-4）参与致敏动物暴露于变应原后引发的肥大细胞活化这一假说。为此，我们研究了用百日咳博德特氏菌作为佐剂对卵清蛋白（OA；皮下注射1毫克）致敏的棕色挪威大鼠。两周后，用OA对大鼠进行激发，测定肺阻力（RL），并测量支气管肺泡灌洗液中组胺和类胰蛋白酶的浓度以及胆汁中N-乙酰白三烯（LT）E4的浓度。用抗VLA-4单克隆抗体（TA-2）预处理可减轻OA激发后的早期反应（基线RL的342.9±24.4%对153.3±19.4%；p<0.01）。TA-2处理的动物中组胺（67.11±11.90微克/毫升对26.69±1.84；p<0.01）和类胰蛋白酶（0.143±0.035微克/毫升对0.053±0.022微克/毫升；p<0.01）的浓度显著更低。TA-2处理的动物中OA激发后胆汁中N-乙酰-LTE4浓度的升高也显著更低。这些数据表明，选择性抗VLA-4单克隆抗体通过抑制肥大细胞活化来预防早期反应。
