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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1166-1174. Prepublished online as a Blood First Edition Paper on April 7, 2008; DOI 10.1182/blood-2007-06-098327.
Submitted June 27, 2007
Department of Ophthamology, University of Aberdeen Institute of Medical Sciences, Aberdeen, United Kingdom * Corresponding author; email: j.liversidge{at}abdn.ac.uk.
Using non-invasive in vivo imaging and experimental autoimmune uveoretinitis as a model we show for the first time, that the mechanisms controlling blood monocyte recirculation through peripheral and lymphoid tissues alter during inflammation. The recirculation of monocytes in mice with ocular inflammation, but not controls was found to be dependent upon CD62-L and CD44. Not only was rolling efficiency ablated or markedly reduced in antibody treated mice, the majority of labelled monocytes disappeared from the circulation within seconds, anti-CD44 treated monocytes homing to the lymph nodes and anti-CD62-L treated monocytes homing to the spleen. Our data indicate that while PSGL-1 has a partial role in the transmigration of monocytes into the inflamed retina, CD62-L has a key role in regulating recruitment of monocytes to lymphoid tissue from the blood during inflammation and that CD44 is required to maintain CD62-L+ve inflammatory monocytes within the circulation during inflammation. This effect was systemic, as sequestered monocytes accumulated in mesenteric as well as draining cervical lymph nodes, and inflammation dependent, as depletion of circulating blood monocytes was much reduced or absent in normal mice and accumulations of adoptively transferred monocytes in the lymphoid tissues did not occur.
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