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A more recent version of this article appeared on December 1, 2006

Published online before print August 31, 2006
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0606388


Received for publication June 9, 2006.
Revised July 18, 2006.
Accepted for publication July 23, 2006.


Article

MD-2 expression is not required for cell surface targeting of Toll-like receptor 4 (TLR4)

Alberto Visintin @, Kristen A. Halmen , Naseema Khan , Brian G. Monks , Douglas T. Golenbock , and Egil Lien

Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester

@ To whom correspondence should be addressed. E-mail: alberto.visintin{at}umassmed.edu.


   Abstract

The cell surface receptor complex formed by TLR4 and myeloid differentiation 2 (MD-2) is engaged when cells are exposed to LPS. Recent studies suggested that surface localization of functional mouse TLR4 (mTLR4) depends on the simultaneous expression of MD-2. As we did not observe a similar requirement, we conducted a comparative study of human TLR4 and mTLR4 surface expression in immune cells derived from the MD-2 knockout mouse and LPS-responsive cell lines and in cells that ectopically express TLR4. Our results indicate that in the human and mouse models, neither TLR4 function nor TLR4 surface targeting requires MD-2 coexpression. Accordingly, we report on one human cell line, which constitutively expresses functional TLR4 on the cell surface in the absence of MD-2 expression.

Key Words: innate immunity • LPS • pathogen recognition




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