Artigo Acesso aberto Revisado por pares

A functional folate receptor is induced during macrophage activation and can be used to target drugs to activated macrophages

2008; Elsevier BV; Volume: 113; Issue: 2 Linguagem: Inglês

10.1182/blood-2008-04-150789

ISSN

1528-0020

Autores

Wei Xia, Andrew R. Hilgenbrink, Eric L. Matteson, Michael B Lockwood, Ji‐Xin Cheng, Philip S. Low,

Tópico(s)

Autoimmune and Inflammatory Disorders Research

Resumo

Abstract 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-α (TNF-α) 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.

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