EXPRESSION OF A LONG PENTRAXIN, PTX3, BY MONOCYTES EXPOSED TO THE MYCOBACTERIAL CELL-WALL COMPONENT LIPOARABINOMANNAN

PTX3 is a prototypic long pentraxin composed of a C-terminal domain si milar to those of classical pentraxins (e.g,, C reactive protein) and an unrelated N-terminal portion, PTX3 is expressed in a variety of cel l types, notably mononuclear phagocytes and endothelial cells, after e xposure to the inflammatory cytokines interleukin-1 beta (IL-1 beta) a nd tumor necrosis factor alpha (TNF-alpha). The present study was desi gned to assess whether mycobacterial components were able to induce ex pression and production of PTX3. Mycobacterial lipoarabinomannan (LAM) induced expression of PTX3 mRNA in human peripheral blood mononuclear cells. The non-mannose-capped version of lipoarabinomannan (AraLAM) w as considerably more potent than the mannose-capped version ManLAM or the simpler version phosphatidylinositol mannoside. Among mononuclear cells, monocytes were responsible for LAM-induced PTX3 mRNA expression . Whole mycobacteria (Mycobacterium bovis BCG) strongly induced PTX3 e xpression. Pretreatment with actinomycin D abolished LAM-induced PTX3 expression, whereas cycloheximide only partially reduced the expressio n. LAM-induced PTX3 expression was associated with the production of i mmunoreactive PTX3, IL-IO and IL-13 did not inhibit the induction of P TX3 by LAM. Under the same conditions, these anti-inflammatory cytokin es inhibited MCP-1 expression. In contrast, gamma interferon inhibited LAM-induced PTX3 expression, Thus, in addition to IL-I, TNF, and lipo polysaccharide, mycobacterial cell wall components also induce express ion and production of the long pentraxin PTX3. The significance of PTX 3 in the immunobiology of mycobacterial infection and its relevance in relation to clinical involvement remain to be determined.