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Aslihan Turhan, Wolfgang A. Schrems, Dimothenes Mantopoulos, Ulrich H. von Andrian, Pedram Hamrah; Dendritic Cell Recruitment to the Cornea is Differentially Regulated in Steady State and Inflammation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1115.
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© ARVO (1962-2015); The Authors (2016-present)
It is now well established that the naïve cornea is endowed with central and peripheral dendritic cells (DC). However the molecules mediating the homing of DC to the cornea are not defined completely. In this study we studied the contribution of selectins and integrins in the rolling and adhesion characteristics of DC in the limbal vasculature.
BALB/c mice were used to study rolling and adhesion in limbal vessels in steady state and suture-induced inflammation. Rolling and adhesion of DC, isolated from the spleen of Ftl3 tumor mice was examined by intravital microscopy (IVM, 500 Mikron Instruments). Effect of adhesion molecules was determined by intravenous injection of antibodies to selectins (P, E and L) and integrins (ICAM-1 and VCAM-1) 30 minutes before IVM recordings or by pre-treatment of DC with relevant ligands.
Our results demonstrate that during steady state, DC rolling on limbal vessel is mediated by P-selectin ( 0.049, p=0.02) and VCAM-1 ( 0.033, p=0.01), but not E- or L-selectins. PSGL-1 treatment of DC also significantly reduces rolling ( 0.02, p=0.04). Interestingly, neither ICAM-1 nor VCAM-1 significantly reduced adhesion in steady state. In contrast, during inflammation, rolling of DC on limbal vessel was mediated by both P- ( 0.000, p< 0.001) and E-selectins ( 0.065, p=0.004), but not L-selectin. Blocking both P- and E-selectins also showed significant ( 0.013, p=0.001) decrease in rolling. Interestingly, none of the cell adhesion molecules tested in the inflamed corneas showed a decrease in DC adhesion.
: IVM demonstrates that while P-selectin and VCAM-1 mediate DC rolling during steady state, during inflammation, rolling is mediated by P- and E-selectins. The fact that none of the tested cell adhesion molecules was involved in adhesion of DC is surprising and suggests the role of other adhesion molecules.Support: NIH K08-EY020575, NIH K12-EY016335, New England Corneal Transplant Research Fund, Falk Medical Research Trust.
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