CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Neutrophil assists the pro-apoptotic activity of SLPI (Secretory leukocyte protease inhibitor) on mammary tumor cell lines
Autor/es:
AMIANO, NICOLÁS; TATEOSIAN, NANCY; PAYÉS, CRISTIAN; ALIJA, ANA; SANCHEZ, MERCEDES; CHULUYAN, EDUARDO
Lugar:
Buenos Aires, Argentina
Reunión:
Congreso; First French Argentine Immunology Congress. LVIII Reunión Anual de la Sociedad Argentina de Inmunología; 2010
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:
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SLPI is an 11.7 kDa protein that plays an important role in protection
against neutrophil proteases during the inflammatory response. In previous
results we demonstrated that SLPI induces apoptosis of mammary tumor cells.
Moreover, we described that mice mammary tumor cells SLPI overexpressing (2C1),
do not develop tumors in Balb/c mice but grow in mice-depleted neutrophils
(PMN). The aim of the present work was to examine the contribution of PMN to
the pro-apoptotic activity of the SLPI. Apoptosis was evaluated by flow
cytometry. Balb/c mice were inoculated or not with 2C1 cells (SLPI
over-expressing cells derived from F3II cells). Plasma from those animals were
obtained at day 2 and 7 post-inoculation and it assessed for apoptosis activity
on 2C1 cells in vitro. Plasma from 2C1 inoculated animals but not control
plasma, induced in vitro apoptosis of 2C1 cells (48h: Control: 37±4%; 2C1
plasma: 55±6%; p<0.05; 7d: Control: 53±10%; 2C1 plasma: 83±12%; p<0.05).
The apoptotic activity of plasma from 2C1-inoculated mice, was partially lost
if animals were previously PMN depleted (Control plasma: 53±12%; PMN depleted
plasma: 14±4%, p<0.01). These results confirmed that the in vivo apoptotic
effect of SLPI is, in part, mediated through PMN. Then, we set up an in vitro
model to test if we can resemble the in vivo situation. For this, human mammary
tumor cell line (MDA-MB231), HeLa (cervix carcinoma) and A549 (lung carcinoma)
were treated with exogenous rhSLPI in the presence of neutrophils. We observed
that PMN increased the apoptosis of the MDA-MB231 induced by SLPI (SLPI: 25±1%;
SLPI + PMN: 30±1%, p<0.05). On the contrary, apoptosis of HeLa and A549
cells were significantly decreased when they were treated with SLPI + PMN
(HeLa: SLPI: 55±5% vs SLPI + PMN: 42±1%, p<0.05; A549: SLPI: 53±1% vs
SLPI+PMN: 44±1%, p<0.05). Overall, these results suggest that the
neutrophils help the pro-apoptotic activity of SLPI on mammary tumor cells but
not on HeLa or A549 cell lines.