INVESTIGADORES
FOSSATI Carlos Alberto
congresos y reuniones científicas
Título:
Brucella abortus infected synoviocytes mediate osteoarticular inflammatory damage through induction of apoptosis and MMPs secretion
Autor/es:
SCIAN R; BARRIONUEVO P,; GIAMBARTOLOMEI GH; FOSSATI, CA; BALDI PC,; DELPINO MV,
Reunión:
Congreso; First French-Argentine Immunology Congress. LVIII Reunión Anual de la Sociedad Argentina de Inmunología; 2010
Resumen:
Osteoarticular
complications are common in human brucellosis, but the pathogenic mechanisms
involved are largely unknown. Matrix metalloproteinases (MMPs) and apoptosis
are involved in joint and bone damage in inflammatory and infectious diseases.
We investigated the production of MMPs by human synoviocytes (line SW982) upon
Brucella abortus infection. Since we had found that Brucella-infected human
synoviocytes produce IL-8 we also analyzed the role of neutrophils in MMP
production and the effects of supernatants from Brucella-infected neutrophils
on synoviocytes and viceversa. The production of MMPs was analyzed by
zymography and ELISA. Infection with B. abortus induced MMP-2 secretion by synoviocytes
(59.63±2.3 ng/ml) and MMP-9 by neutrophils (54.4±2.9 ng/ml). In both cell types
MMPs were induced by L-Omp19 lipoprotein from B. abortus (synoviocytes:
92.2±1.4; neutrophils 61.2±1 ng/ml) and in synoviocytes this induction was
mediated by TLR-2.As mentioned, Brucella-infected synoviocytes may attract
neutrophils to the site of infection. Thus, we decided to study the effects of
cytokines secreted by infected neutrophils on the production of MMPs by
synoviocytes and viceversa. Supernatants from Brucella-infected neutrophils
induced a significant secretion of MMP-2 (70.1±10.6 ng/ml) by synoviocytes
cells as compared with supernatants from uninfected neutrophils. In addition,
supernatants from infected synoviocytes induced the production of MMP-9 on uninfected
neutrophils. Brucella-infection or L-Omp19 stimulation also induced synoviocyte
apoptosis as measured by fluorescence microscopy analysis of TUNEL and Hoechst
33342 reactions (Brucella-infected: 40% and 25% apoptotic cells, respectively;
L-Omp19 stimulation: 30% and 18%; untreated: 5% and 3%). These results indicate
that host-derived MMPs and apoptosis could contribute to the progressive joint
destruction observed in Brucella infection.