ICMI 2015

F.71 CLEAREANCE OF PTX3 PRE-OPSONIZED CONIDIA OF A. FUMIGATUS FROM THE LUNG  OF RATS IMMUNOSUPPRESSED BY CORTISONE ACETATE

Friday, July 17, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Giovanni Salvatori , Sigma-Tau S.p.A., POMEZIA, ROME, Italy
CLEAREANCE OF PTX3 PRE-OPSONIZED CONIDIA OF A. FUMIGATUS FROM THE LUNG  OF RATS IMMUNOSUPPRESSED BY CORTISONE ACETATE

Emanuele Marra1, Brunilde Arseni1, Lucrezia Pacello1, Roberta Gaziano2 ,  Caterina Chiapparino3, Rita De Santis3 and Giovanni Salvatori3

1 Takis srl, Via di Castel Romano 100, Rome, Italy ; 2University of Tor Vergata, Rome, Italy;  3Sigma-tau  S.pA. R&D Biotechnology, Via Pontina, km 30,400, Pomezia , 00040, Italy

PTX3 is multimeric glycoprotein that  binds to  A. fumigatus  and promotes phagocytosis and killing of conidia by innate immunity cells, a process  defined as opsonization.

In order to provide proof of concept that direct administration of PTX3 to the respiratory mucosa would preserve protein mediated clearance of A. fumigatus from the lung of rats immunosuppressed by cortisone acetate, PTX3 pre-opsonized conidia were intra-tracheal administered in these animals. Three PTX3 concentrations were selected for the in vivo study corresponding to saturation, intermediate and low binding of PTX3 to conidia. Twenty four hours after intra-tracheal administration with 5x107pre-opsonized conidia, rats were sacrificed and fungal burden evaluated in lung and blood by CFU and galactomannan (GMI) respectively.

The rats challenged with PTX3-saturated conidia, showed similar CFU and GMI compared to rats challenged with PTX3-free conidia. A reduction of lung CFU was observed in rats infected with intermediate and low PTX3 concentrations suggesting a pro-zone effect in the mechanisms of opsonization. Present results are consistent with PTX3 opsonic activity  and suggest that local administration of PTX3 on the respiratory mucosa, for instance by aerosol, could be useful but  dose selection should be carefully identified.