Purchase this article with an account.
Aslihan Turhan, Takefumi Yamaguchi, Ulrich H. von Andrian, Pedram Hamrah; Mucosal Addressin Cell Adhesion Molecule (MAdCAM)-1 Plays a Pivotal Role in Dendritic Cell Recruitment to the Cornea During Inflammation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3140.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The cornea is endowed with resident dendritic cells (DC). We have recently shown that vascular cell adhesion molecule (VCAM)-1 and P-selectin mediate, in part, DC recruitment to the cornea. This study aims to analyze the role of MAdCAM-1, a molecule previously not described on the ocular surface, on DC homing to cornea.
Rolling and adhesion of adoptively transferred fluorescently-labeled DC were studied in limbal vessels of BALB/c mice by intravital microscopy (IVM, 500 Mikron Instruments) in steady state and suture-induced inflammation in vivo. Anti-MAdCAM-1 blocking antibody or controls antibody were injected intravenously (i.v.) 30 minutes before IVM recordings. Separately, DC were treated with blocking antibodies to MAdCAM-1 ligands α4β7 or L-Selectin prior to injection. Homing (recruitment) of DC to normal or inflamed corneas were studied by ex vivo confocal microscopy (Olympus Fluoview 1000) 24 hours after i.v. injection of fluorescently-labeled DC. Flow cytometry studies were performed on DC, purified by magnetic cell separation and analysed for DC markers and MAdCAM-1 ligands.
Blockade of MAdCAM-1 or L-selectin did not affect DC rolling or adhesion during steady state compared to controls (p=0.23). However, MAdCAM-1 significantly reduced the rolling fraction in inflamed corneas (4.1 %) as compared to controls (20.7%; p< 0.001). Further, anti-MAdCAM-1 treatment profoundly reduced the sticking efficiency of DC during inflammation (0.4%) compared to controls (3.4%; p< 0.001).Homing experiments with blockade of anti-MAdCAM-1 (18.4 cells/mm2; p=0.005) or its ligand α4β7 (4.5 cells/mm2; p=0.003), α4 (12.1 cells/mm2, p=0.032) and β7 (3.2 cells/mm2, p=0.007), showed significant reduction of DC homing to the inflamed cornea as compared to controls (51.5 cells/mm2). Flow cytometry confirmed expression of both α4β7 and L-selectin on CD11c-high DC.
We demonstrate, for the first time, a role of MAdCAM-1 in leukocyte recruitment to the cornea through limbal vessels. MAdCAM-1 mediates rolling and sticking of DC during inflammation, but not in steady state. MAdCAM-1 or its ligands may provide new molecular targets for pharmacological intervention in inflammatory, infectious, alloimmune and autoimmune corneal diseases.
This PDF is available to Subscribers Only