Journal
BLOOD
Volume 113, Issue 2, Pages 438-446Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-04-150789
Keywords
-
Categories
Funding
- Endocyte (West Lafayette, IN)
Ask authors/readers for more resources
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-alpha (TNF-alpha) 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. (Blood. 2009;113:438-446)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available