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Bone Marrow-derived Macrophage Production
Published on: November 22, 2013
Expression of a long pentraxin, PTX3, by monocytes exposed to the mycobacterial cell wall component lipoarabinomannan
V Vouret-Craviari1, C Matteucci, G Peri
1Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Abstract:
PTX3 is a prototypic long pentraxin composed of a C-terminal domain similar to those of classical pentraxins (e.g., C reactive protein) and an unrelated N-terminal portion. PTX3 is expressed in a variety of cell types, notably mononuclear phagocytes and endothelial cells, after exposure to the inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha). The present study was designed to assess whether mycobacterial components were able to induce expression 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) was 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 expression. Pretreatment with actinomycin D abolished LAM-induced PTX3 expression, whereas cycloheximide only partially reduced the expression. LAM-induced PTX3 expression was associated with the production of immunoreactive PTX3. IL-10 and IL-13 did not inhibit the induction of PTX3 by LAM. Under the same conditions, these anti-inflammatory cytokines inhibited MCP-1 expression. In contrast, gamma interferon inhibited LAM-induced PTX3 expression. Thus, in addition to IL-1, TNF, and lipopolysaccharide, mycobacterial cell wall components also induce expression and production of the long pentraxin PTX3. The significance of PTX3 in the immunobiology of mycobacterial infection and its relevance in relation to clinical involvement remain to be determined.
Insights
Mycobacterial components, such as lipoarabinomannan (LAM), stimulate the production of PTX3 (long pentraxin) in human immune cells. This finding highlights a new pathway in the immune response to mycobacterial infections.
Area of Science:
- Immunology
- Molecular Biology
Background:
- PTX3 is a long pentraxin involved in innate immunity.
- PTX3 expression is induced by inflammatory cytokines like IL-1beta and TNF-alpha.
- Its role in mycobacterial infections is not well understood.
Purpose of the Study:
- To investigate whether mycobacterial components can induce PTX3 expression and production.
- To identify specific mycobacterial components responsible for PTX3 induction.
- To explore the cellular and molecular mechanisms underlying PTX3 induction by mycobacteria.
Main Methods:
- Human peripheral blood mononuclear cells (PBMCs) were treated with various mycobacterial components, including lipoarabinomannan (LAM) and whole Mycobacterium bovis BCG.
- PTX3 mRNA expression was quantified using RT-PCR.
- Protein production was assessed by measuring immunoreactive PTX3.
- The role of transcription and translation was investigated using actinomycin D and cycloheximide.
- The effect of cytokines (IL-10, IL-13, IFN-gamma) on PTX3 induction was evaluated.
Main Results:
- Mycobacterial lipoarabinomannan (LAM) significantly induced PTX3 mRNA expression in human PBMCs.
- The non-mannose-capped AraLAM was more potent than ManLAM or phosphatidylinositol mannoside.
- Monocytes were the primary cells responsible for LAM-induced PTX3 expression.
- Whole Mycobacterium bovis BCG also strongly induced PTX3 expression.
- LAM-induced PTX3 expression was dependent on new transcription but not significantly on de novo protein synthesis.
- PTX3 protein production was associated with LAM induction.
- Anti-inflammatory cytokines IL-10 and IL-13 did not inhibit LAM-induced PTX3, unlike MCP-1.
- Gamma interferon inhibited LAM-induced PTX3 expression.
Conclusions:
- Mycobacterial cell wall components, particularly LAM, are potent inducers of PTX3 expression and production in human immune cells.
- This suggests a novel role for PTX3 in the innate immune response to mycobacteria.
- The differential regulation by cytokines warrants further investigation into PTX3's specific function in mycobacterial infections.
