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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.

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IMMUNOBIOLOGY

Critical but divergent roles for CD62L and CD44 in directing blood monocyte trafficking in vivo during inflammation

Heping Xu1, Ayyakkannu Manivannan2, Isabel Crane1, Rosemary Dawson1, and Janet Liversidge1

1 Department of Ophthalmology, University of Aberdeen Institute of Medical Sciences, Aberdeen; and 2 Department of Radiology, University of Aberdeen, Aberdeen, United Kingdom

Using noninvasive 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 depend on the selectin CD62-ligand (CD62L) and on CD44. Not only was rolling efficiency ablated or markedly reduced in antibody-treated mice, but most of the labeled monocytes also disappeared from the circulation within seconds, anti-CD44–treated monocytes homing to the lymph nodes and anti–CD62L-treated monocytes homing to the spleen. Our data indicate that, although PSGL-1 has a partial role in the transmigration of monocytes into the inflamed retina, CD62L has a key role in regulating recruitment of monocytes to lymphoid tissue from the blood during inflammation and that CD44 is required to maintain CD62L+ inflammatory monocytes within the circulation during inflammation. This effect was systemic, because sequestered monocytes accumulated in mesenteric as well as draining cervical lymph nodes, and inflammation dependent, because 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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Related Article in Blood Online:

Teasing out monocyte trafficking mechanisms
Christopher V. Carman
Blood 2008 112: 929-930. [Full Text] [PDF]



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A. Dagkalis, C. Wallace, H. Xu, S. Liebau, A. Manivannan, M. A. Stone, M. Mack, J. Liversidge, and I. J. Crane
Development of Experimental Autoimmune Uveitis: Efficient Recruitment of Monocytes Is Independent of CCR2
Invest. Ophthalmol. Vis. Sci., September 1, 2009; 50(9): 4288 - 4294.
[Abstract] [Full Text] [PDF]


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