CLONING OF MOUSE PTX3, A NEW MEMBER OF THE PENTRAXIN GENE FAMILY EXPRESSED AT EXTRAHEPATIC SITES

Pentraxins, which include C reactive protein (CRP) and serum amyloid P component (SAP), are prototypic acute phase reactants that serve as i ndicators of inflammatory reactions. Here we report genomic and cDNA c loning of mouse ptx3 (mptx3), a member of the pentraxin gene family an d characterize its extrahepatic expression in vitro and in vivo. mptx3 is organized into three exons on chromosome 3: the first (43 aa) and second exon (175 aa) code for the signal peptide and for a protein por tion with no high similarity to known sequences, the third (203 aa) fo r a domain related to classical pentraxins, which contains the ''pentr axin family signature.'' Analysis of the N terminal portion predicts a predominantly cu helical structure, while the pentraxin domain of ptx 3 is accommodated comfortably in the tertiary structure fold of SAP. N ormal and transformed fibroblasts, undifferentiated and differentiated myoblasts, normal endothelial cells, and mononuclear phagocytes expre ss mptx3 mRNA and release the protein in vitro on exposure to interleu kin-1 beta (IL-1 beta) and tumor necrosis factor (TNF)alpha . mptx3 wa s induced by bacterial lipopolysaccharide in vivo in a variety of orga ns and, most strongly, in the vascular endothelium of skeletal muscle and heart. Thus, mptx3 shows a distinct pattern of in vivo expression indicative of a significant role in cardiovascular and inflammatory pa thology. (C) 1996 by The American Society of Hematology.