Role of VLA-4 in the development of allergic conjunctivitis inmice

[摘要] Purpose: The severity of allergic conjunctivitis (AC) correlateswith the degree of eosinophil infiltration into the conjunctiva, whichis believed to be mediated by chemokines and adhesion molecules. Theadhesion molecule very late antigen (VLA)-4 and its ligand, vascularcell adhesion molecule (VCAM)-1, are known to play important roles ineosinophil infiltration. However, the expression and function of VLA-4in AC have not been investigated in detail. We sought to characterizeVLA-4-expressing cells in the conjunctivas of mice that are developingexperimental AC (EC) and to determine whether the interaction betweenVLA-4 and VCAM-1 is needed for the infiltration of eosinophils into theconjunctiva in AC.Methods: EC was induced in Balb/c mice by active immunization withragweed (RW) or adoptive transfer of RW-primed splenocytes, followed byRW challenge. Twenty-four hours after RW challenge, the conjunctivaswere harvested. The conjunctivas from naive mice or mice developing ECwere evaluated for VLA-4 and VCAM-1 expression by immunohistochemistryand immunofluorescent analyses. To investigate whether the interactionbetween VLA-4 and VCAM-1 is needed for the genesis of AC, micedeveloping EC were treated with anti-VLA-4 or anti-VCAM-1 antibodies twoh before and after RW challenge. As a control, EC-developing mice weretreated with normal rat IgG. Twenty-four hours after RW challenge, theconjunctivas were harvested for histological analysis.Results: Upon induction of EC, VLA-4-expressing cells infiltratedthe conjunctiva but the constitutive VCAM-1 expression aroundconjunctival vessels was not augmented. Immunofluorescent analysesdemonstrated that most of the T cells infiltrating the conjunctivaexpressed VLA-4 but only half of the infiltrating eosinophils expressedit. Treatment with both anti-VLA-4 and anti-VCAM-1 antibodiessignificantly suppressed the infiltration of eosinophils into theconjunctiva that was induced by either active immunization or splenocytetransfer.Conclusions: These results confirm that VLA-4-expressing cellsinfiltrate the conjunctiva and that the interaction between VLA-4 andVCAM-1 is needed for the development of EC.

[学科分类] 生物化学/生物物理