Lipopolysaccharide of Burkholderia cepacia and its unique character to stimulate murine macrophages with relative lack of interleukin-1 beta-inducingability

Lipopolysaccharide (LPS) of Burkholderia cepacia was purified by the conven tional phenol-water extraction method (preparation BcLPS-1), followed by en zymatic treatments with DNase, RNase, trypsin, and proteinase K (preparatio n BcLPS-2), and finally by deoxycholate-phenol-water extraction (preparatio n BcLPS-3). Cells of LPS-hyporesponsive C3H/HeJ mice were activated by both the BcLPS-1 and the BcLPS-2 preparations but barely activated by BcLPS-3. When LPS-responsive C3H/HeN mice were used as targets, endotoxic activities such as lethal toxicity to galactosamine-sensitized mice, mitogenicity to spleen cells, and activation of macrophages to induce tumor necrosis factor alpha and interleukin-6 (IL-6) were strongly exhibited even by highly puri fied BcLPS-3 at levels comparable to those of the highly active enterobacte rial LPS of Salmonella enterica serovar Abortus-equi (SaeLPS), used as the control. The ability of BcLPS-3 to activate murine macrophages for inductio n of IL-1 beta was, however, much weaker than that of SaeLPS. Both accumula tion of pro-IL-1 beta protein and expression of IL-1 beta mRNA in macrophag es by stimulation with BcLPS-3 were much weaker than by stimulation with Sa eLPS. These results indicate that LPS of B. cepacia has the potential to pl ay a role as a pathogenic factor,vith strong activity comparable to that of usual enterobacterial LPS, but unlike the latter, this LPS has a relative lack of ability in the activation of murine macrophages to induce IL-1 beta . The lack of IL-1 beta -inducing ability appears to be caused by incomplet e signal transduction somewhere in the upstream step(s) of IL-1 beta gene t ranscription.