Depletion of synovial macrophages in rheumatoid arthritis by an anti-FcgammaRI-calicheamicin immunoconjugate.
Ann Rheum Dis
; 64(6): 865-70, 2005 Jun.
Article
en En
| MEDLINE
| ID: mdl-15539412
ABSTRACT
BACKGROUND:
Monocytes/macrophages have an important and versatile role in joint inflammation and destruction in rheumatoid arthritis (RA).OBJECTIVE:
To determine the efficiency of monocyte/macrophage elimination by a new drug conjugated antibody (CD64-calicheamicin (CD64-CaMi)) directed to the high affinity receptor for IgG (FcgammaRI).METHODS:
Mononuclear cells from peripheral blood and synovial fluid of patients with RA were cultured in the presence of CD64-CaMi. Cell death of monocytes/macrophages was measured by analysis of phenotypic changes (light scatter patterns, CD14 expression, and FcgammaRI expression) and nuclear DNA fragmentation. The selectivity of CD64-CaMi was checked by using FcgammaRI deficient and FcgammaRI transfected cell lines. In addition, the indirect effect of CD64-CaMi-induced macrophage cell death on arthritogenic T(h1) cell activity was determined.RESULTS:
Inflammatory macrophages from RA synovial fluid, expressing increased FcgammaRI levels, were efficiently killed by CD64-CaMi through induction of DNA fragmentation. CD64-CaMi-induced cell death of monocytes/macrophages from peripheral blood of patients with RA proved less efficient. Induction of synovial macrophage death by CD64-CaMi was accompanied by efficient inhibition of proinflammatory T(h1) cytokine production.CONCLUSION:
Together, the presented data suggest that elimination of macrophages through a new FcgammaRI directed CD64-CaMi is feasible. Because monocytes from peripheral blood are also eliminated by this immunoconjugate, additional experimental studies should validate its potential for local (intra-articular) application in the treatment of RA.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
/
Líquido Sinovial
/
Inmunoconjugados
/
Macrófagos
Límite:
Aged
/
Aged80
/
Humans
/
Middle aged
Idioma:
En
Revista:
Ann Rheum Dis
Año:
2005
Tipo del documento:
Article
País de afiliación:
Países Bajos