| First Author | Xia W | Year | 2009 |
| Journal | Blood | Volume | 113 |
| Issue | 2 | Pages | 438-46 |
| PubMed ID | 18952896 | Mgi Jnum | J:144860 |
| Mgi Id | MGI:3832111 | Doi | 10.1182/blood-2008-04-150789 |
| Citation | Xia W, et al. (2009) A functional folate receptor is induced during macrophage activation and can be used to target drugs to activated macrophages. Blood 113(2):438-46 |
| abstractText | 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. |
