Inducible expression of the long pentraxin PTX3 in the central nervous system

PTX3 is a prototypic long pentraxin consisting of a C terminal 203-amino ac id pentraxin-like domain coupled with an N-terminal 178-amino acid unrelate d portion. PTX3 is induced by primary proinflammatory signals in various ce ll types, most prominently macrophages and endothelial cells. Other long pe ntraxins, such as murine or rat neuronal pentraxin 1 (NP1) and human neuron al pentraxin 2 (NPTX2), are expressed in the central nervous system (CNS). The present study was designed to investigate whether PTX3 is expressed in the brain and to define the structures and cells involved. Intracerebrovent ricular (i.c.v.), but not i.v., injection of LPS induced high levels of PTX 3 mRNA in the mouse brain. In contrast NP1 is constitutively expressed in t he murine CNS and is not modulated by LPS administration. I.c.v. IL-1 beta was also a potent inducer of PTX3 expression in the CNS, whereas TNF alpha was substantially less effective and IL-6 induced a barely detectable signa l. Central administration of LPS and IL-1 induced PTX3 also in the peripher y (heart), whereas the reverse did not occur. Expression of PTX3 was also o bserved in the brain of mice infected with Candida albicans (C. albicans) o r Cryptococcus neoformans. (C. neoformans). The kinetics of PTX3 gene induc tion were consistently different between C. albicans- and C. neoformans-inf ected mice, according to the diverse outcome of the CNS immune reaction. In situ hybridization revealed that i.c.v. injection of LPS induced a strong PTX3 expression in presumptive glial cells, in the white matter (corpus cal losum, fimbria) and meningeal pia mater as well as in dentate gyrus hilus a nd granule cells. No constitutive expression of PTX3 was detected. Central expression of PTX3 may amplify mechanisms of innate resistance and damage i n the CNS. The possibility of a direct interaction of PTX3 with neuronal ce lls, as suggested for NPTX2, remains to be explored. (C) 2000 Elsevier Scie nce B.V. All rights reserved.