LOX-1 Regulates Adhension Molecule Expression In A Fumigatus Keratitis

Objective:To determine whether lectin-like ox-LDL receptor(LOX-1)regulates adhesion molecule expressionin A.fumigatus keratitis of C57BL/6 mice.Methods:Corneal response to infection was assessed by clinical score.The adhesion molecule m RNA levels of ICAM-1,VCAM-1,P-selectin,E-selectin and IL-8 was tested in normal and infected cornea of C57BL/6 mice.B6 mice were treated with LOX-1 neutralizing antibody or LOX-1 inhibitor Ploy I,and RT-PCR was used to test levels of adhesion molecule m RNA in corneas of infected with A.fumigatus.The protein level of ICAM-1 was evaluated by immunofluorescent staining and western blotting.Neutrophils were extracted from C57BL/6 mice,and pretreated with LOX-1 neutralizing antibody or Ig G;LOX-1 inhibitor Poly I or PBS,then stimulated with A.fumigatus.The m RNA levels of LFA-1 was evaluated by Real-Time RT-PCR and western blotting were performed to evaluate LFA-1 protein expression.Immunofluorescence and MPO assays were used to test neutrophils infiltration of C57BL/6 mice corneas.Results: Treatment with LOX-1 neutralizing antibody or Ploy I reduced the clinical score of fungal keratitis compared with treatment with control Ig G or control PBS.ICAM-1,VCAM-1,P-selectin,E-selectin and IL-8m RNA were higher in C57BL/6 mice infected corneas than normal corneas.After treatment with LOX-1 neutralizing antibody or LOX-1 inhibitor Ploy I,the expression of ICAM-1,VCAM-1,P-selectin,E-selectin and IL-8 m RNA were significantly decreased compared with treatment with control Ig G or control PBS.After treatment with LOX-1 neutralizing antibody or LOX-1 inhibitor Ploy I,protein level for ICAM-1 was decreased compared with treatment of control Ig G or control PBS.LFA-1 m RNA and protein level were significantly decreased after treatment with LOX-1 neutralizing antibody or LOX-1 inhibitor Ploy I compared with Ig G or PBS controlin C57BL/6 mice neutrophils.Neutrophils infiltration was significantly decreased after treatment of LOX-1 neutralizing antibody or LOX-1 inhibitor Ploy I compared with Ig G or PBS control in cornea.Conclusions: These data provided evidence that LOX-1 can affect the expression of adhesion molecule and neutrophils infiltration in fungal infected corneas of C57BL/6 mice.