PURPOSE: To determine the contribution of very late activation antigen-4 (VLA-4) molecule to eosinophil infiltration into the conjunctiva in an actively sensitized allergic conjunctivitis model of guinea pig, effects of a monoclonal antibody against VLA-4 was examined in vivo. METHODS: A rat anti-mouse VLA-4 mAb (PS 2. 3), which cross-reacts with guinea pig VLA-4, inhibited the adhesion and transmigration of guinea pig eosinophils to /through human umbilical vein endothelial cells (HUVEC) in vitro. Hartley guinea pigs were actively sensitized by intraperitoneal injection of ovalbumin with aluminum hydroxide. Two weeks later, 2.5% ovalbumin was dropped into the eye for the antigen challenge. In the treatment group, 4 mg/kg (body weight) of the anti VLA-4 mAb (PS2.3), and in the control group, the same amount of a control Ab was intraperitoneally injected respectively at 4 hours before the antigen challenge. From both groups, the eyelids and eyeballs were excised at 2, 4, 10, and 24 hours after the antigen challenge, fixed, stained with Hansel solution and the number of the infiltrating eosinophils in the conjunctiva was counted. RESULTS: In the control group, infiltration of eosinophils to the conjunctiva increased with time, peaked at 12 hours, and then gradually decreased until 24 hours after the antigen challenge. In the anti VLA4-mAb treated group, eosinophil infiltration was almost completely inhibited at least until 24 hours after the antigen challenge. CONCLUSION: VLA-4 molecule was elucidated to play a critical roll in the eosinophil infiltration in experimentally-induced allergic conjunctivitis model of guinea pig.
PURPOSE: To determine the contribution of very late activation antigen-4 (VLA-4) molecule to eosinophil infiltration into the conjunctiva in an actively sensitized allergic conjunctivitis model of guinea pig, effects of a monoclonal antibody against VLA-4 was examined in vivo. METHODS: A rat anti-mouse VLA-4 mAb (PS 2. 3), which cross-reacts with guinea pig VLA-4, inhibited the adhesion and transmigration of guinea pig eosinophils to /through human umbilical vein endothelial cells (HUVEC) in vitro. Hartley guinea pigs were actively sensitized by intraperitoneal injection of ovalbumin with aluminum hydroxide. Two weeks later, 2.5% ovalbumin was dropped into the eye for the antigen challenge. In the treatment group, 4 mg/kg (body weight) of the anti VLA-4 mAb (PS2.3), and in the control group, the same amount of a control Ab was intraperitoneally injected respectively at 4 hours before the antigen challenge. From both groups, the eyelids and eyeballs were excised at 2, 4, 10, and 24 hours after the antigen challenge, fixed, stained with Hansel solution and the number of the infiltrating eosinophils in the conjunctiva was counted. RESULTS: In the control group, infiltration of eosinophils to the conjunctiva increased with time, peaked at 12 hours, and then gradually decreased until 24 hours after the antigen challenge. In the anti VLA4-mAb treated group, eosinophil infiltration was almost completely inhibited at least until 24 hours after the antigen challenge. CONCLUSION: VLA-4 molecule was elucidated to play a critical roll in the eosinophil infiltration in experimentally-induced allergic conjunctivitis model of guinea pig.
Authors: B E Theien; C L Vanderlugt; T N Eagar; C Nickerson-Nutter; R Nazareno; V K Kuchroo; S D Miller Journal: J Clin Invest Date: 2001-04 Impact factor: 14.808