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Blood, 8 January 2009, Vol. 113, No. 2, pp. 438-446. Prepublished online as a Blood First Edition Paper on October 24, 2008; DOI 10.1182/blood-2008-04-150789. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-04-150789v1 113/2/438    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Xia, W. Articles by Low, P. S. Search for Related Content PubMed PubMed Citation Articles by Xia, W. Articles by Low, P. S. Related Collections Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS A functional folate receptor is induced during macrophage activation and can be used to target drugs to activated macrophages Wei Xia*,1, Andrew R. Hilgenbrink*,1, Eric L. Matteson2, Michael B. Lockwood3, Ji-Xin Cheng1,4, and Philip S. Low1 1 Department of Chemistry, Purdue University, West Lafayette, IN; 2 Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN; 3 Department of Rheumatology, Clarian Arnett Health, Lafayette, IN; and 4 Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN Previous work has demonstrated that a subset of macrophages expresses a folate receptor (FR) that can mediate internalization of folate-linked molecules, including imaging and therapeutic agents. To characterize this subset, macrophages were collected from peritoneal cavities of mice injected with saline, thioglycolate, zymosan, heat-killed or live bacteria, and cell-surface markers that coexpress with FR were identified. Virtually no F4/80+ peritoneal macrophages from saline-injected mice expressed FR, whereas numerous macrophages from mice injected with each inflammatory stimulus expressed FR. Examination of cell differentiation antigens that are up-regulated in FR+ macrophages revealed markers characteristic of an activated state (CD80, CD86, Ly-6C/G), whereas macrophages lacking these activation markers expressed few or no FR. FR+ macrophages also produced tumor necrosis factor- (TNF-) and reactive oxygen species, and production of reactive oxygen species correlated linearly with expression of FR. Synovial macrophages collected from arthritic patients were found to bind and internalize folate-linked dyes. Moreover, a folate-linked radioimaging agent was shown to image inflamed joints of rheumatoid arthritic patients. These results suggest that FR constitutes a marker for macrophage activation and that FR+ macrophages can be targeted with folate-linked drugs without promoting drug uptake by nonactivated macrophages. This trial was registered at www.clinicaltrials.gov as #NCT00588393 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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