Lipopolysaccharide (LPS) from Burkholderia cepacia is more active than LPS from Pseudomonas aeruginosa and Stenotrophomonas maltophilia in stimulating tumor necrosis factor alpha from human monocytes

Abstract

Whole cells and lipopolysaccharides (LPSs) extracted from Burkholderia cepacia, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Escherichia coli were compared in their ability to stimulate tumor necrosis factor alpha (TNF-alpha) from the human monocyte cell line MonoMac-6. B. cepacia LPS, on a weight-for-weight basis, was found to have TNF-alpha-inducing activity similar to that of LPS from E. coli, which was approximately four- and eightfold greater than the activity of LPSs from P. aeruginosa and S. maltophilia, respectively. The LPS-stimulated TNF-alpha production from monocytes was found to be CD14 dependent. These results suggest that B. cepacia LPS might play a role in the pathogenesis of inflammatory lung disease in cystic fibrosis, and in some patients it might be responsible, at least in part, for the sepsis-like cepacia syndrome.

FIG. 1

Dose response of LPS-induced TNF-α production from stimulated MM6 cells. MM6 cells (10⁶/ml) were incubated with 0.1 to 500 ng of LPS per ml, and TNF-α production was measured by an ELISA. The TNF-α produced was proportional to the LPS concentration up to an LPS dose of 500 ng/ml. Bars represent the mean (+ standard error) of four separate experiments.

FIG. 2

TNF-α production by MM6 cells stimulated by whole bacteria and the extracted LPS. The bars show the mean (+ standard error) of TNF-α production in response to the different LPS types (number of different isolates = 4 to 10 in each group) from four separate experiments. ∗, P = 0.021; ∗∗, P = 0.0054; ∗∗∗, P = 0.00012 (all versus results for B. cepacia [B.cep.] CF isolates). P.aerug, P. aeruginosa; S.malto, S. maltophila.

FIG. 3

Production of TNF-α from MM6 cells stimulated with B. cepacia LPS (500 ng/ml) and in the presence of the anti-CD14 monoclonal antibodies MY4 and UCHM-1 and the MY4 isotype control anti-CD7. ∗∗, P = 0.0004 versus results for LPS alone. IgG, immunoglobulin G.