Polymyxin B Prevents Lipopolysaccharide-Induced Release of Tumor Necrosis Factor-  from Alveolar Macrophages

Stokes, Dennis C.; Shenep, Jerry L.; Fishman, Marvin A.; Hildner, William K.; Bysani, G. Kris; Rufus, K Guthrie

doi:10.1093/infdis/160.1.52

Cited by 80 publications

(34 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is an especially problematic issue with BCC since polymyxin B, a substance normally used to abrogate endotoxic activity (44), lacks affinity for BCC endotoxin (45). To ensure that contaminating endotoxin was not responsible for the EPS effects, we used purified endotoxin as a control.…”

Section: Discussionmentioning

confidence: 99%

Exopolysaccharides from Burkholderia cenocepacia Inhibit Neutrophil Chemotaxis and Scavenge Reactive Oxygen Species

Bylund

Burgess

Cescutti

et al. 2006

Journal of Biological Chemistry

135

View full text Add to dashboard Cite

Bacteria belonging to the Burkholderia cepacia complex are important opportunistic pathogens in compromised hosts, particularly patients with cystic fibrosis or chronic granulomatous disease. Isolates of B. cepacia complex may produce large amounts of exopolysaccharides (EPS) that endow the bacteria with a mucoid phenotype and appear to facilitate bacterial persistence during infection. We showed that EPS from a clinical B. cenocepacia isolate interfered with the function of human neutrophils in vitro; it inhibited chemotaxis and production of reactive oxygen species (ROS), both essential components of innate neutrophil-mediated host defenses. These inhibitory effects were not due to cytotoxicity or interference with intracellular calcium signaling. EPS also inhibited enzymatic generation of ROS in cell-free systems, indicating that it scavenges these bactericidal products. B. cenocepacia EPS is structurally distinct from Pseudomonas aeruginosa alginate, yet they share the capacity to scavenge ROS and inhibit chemotaxis. These properties could explain why the two bacterial species resist clearance from the infected cystic fibrosis lung.

show abstract

Section: Discussionmentioning

confidence: 99%

Exopolysaccharides from Burkholderia cenocepacia Inhibit Neutrophil Chemotaxis and Scavenge Reactive Oxygen Species

Bylund

Burgess

Cescutti

et al. 2006

Journal of Biological Chemistry

135

View full text Add to dashboard Cite

show abstract

“…When polymyxin B, a cationic peptide that blocks the biological function of LPS (46), was added to the cultures, it did not inhibit cytokine secretion (data not shown). This suggests that the cytokine-inducing responses observed with the various LM preparations could not be attributed to an eventual LPS contamination.…”

Section: Lms But Not Lams Induce Secretion Of Proinflammatory Cytokmentioning

confidence: 97%

Lipomannans, But Not Lipoarabinomannans, Purified fromMycobacterium chelonaeandMycobacterium kansasiiInduce TNF-α and IL-8 Secretion by a CD14-Toll-Like Receptor 2-Dependent Mechanism

Vignal

Guérardel

Kremer

et al. 2003

The Journal of Immunology

125

131

View full text Add to dashboard Cite

Lipoarabinomannans (LAMs) are glycolipids from the mycobacterial cell wall that exhibit various biological activities, including proinflammatory and anti-inflammatory responses. However, little is known about the properties of lipomannans (LMs), considered to be precursors of LAMs. In this study, we provide evidence that LMs purified from Mycobacterium chelonae and a clinical strain of Mycobacterium kansasii stimulated mRNA expression and secretion of TNF-α and IL-8 from human macrophage-like differentiated THP-1 cells. In contrast to LMs, LAMs were not able to induce a significant cytokine-inducing effect. The mechanism of activation by LMs was investigated using various Abs raised against surface receptors for multiple bacterial products. The presence of anti-CD14 or anti-Toll-like receptor 2 (TLR2) Abs profoundly affected production of TNF-α and IL-8, suggesting that both CD14 and TLR2 participate in the LM-mediated activation process. Furthermore, stimulation of cells was dependent on the presence of the LPS-binding protein, a plasma protein that transfers glycolipids to CD14. Chemical degradation of the arabinan domain of mannose-capped LAM from M. kansasii, which presented no cytokine-eliciting effect, restored the cytokine-inducing activity at a level similar to those of LMs. These results support the hypothesis that the presence of an arabinan in LAMs prevents the interaction of these glycolipids with TLR2/CD14 receptors. In addition, we found that phosphatidylinositol dimannosides isolated from M. kansasii did not induce cytokine secretion. This study suggests that LMs isolated from different mycobacterial species participate in the immunomodulation of the infected host and that the d-mannan core of this glycolipid is essential for this function.

show abstract

“…It has been well established that PmxB has high affinity for negatively charged bacterial cell surface components, including LPS, and that its binding to LPS plays an essential role in its bactericidal activity (32). PmxB is also known as a potent LPS antagonist which suppresses various biological activities of LPS, such as lethal toxicity and induction of cytokines, by forming PmxB-LPS complexes with electrostatic and hydrophobic interactions (7,26,31). The presence of Ara4N with a positive charge that reduces the electronegativity of LPS is considered to be re-sponsible for the decreased binding of PmxB, causing LPS to be resistant to the antagonistic action of PmxB.…”

mentioning

confidence: 99%

Unusual Interaction of a Lipopolysaccharide Isolated fromBurkholderia cepaciawith Polymyxin B

et al. 2003

View full text Add to dashboard Cite

We have demonstrated that lipopolysaccharide (LPS) obtained from Burkholderia cepacia, an important opportunistic pathogen, has unique characteristics in both structure and activity. One of the structural characteristics is that the B. cepacia LPS has 4-amino-4-deoxy-L-arabinose (Ara4N) in its inner core region. Polymyxin B (PmxB) is known to act as an LPS antagonist, but LPS with Ara4N is suggested to be PmxB resistant by decreasing the binding capability of PmxB. Interaction of B. cepacia LPS with PmxB was investigated and compared with that of a reference LPS of Salmonella enterica serovar Abortusequi, referred to hereafter as the reference LPS. B. cepacia LPS suffered no suppressive effect of PmxB in its activity to stimulate murine peritoneal macrophages for induction of tumor necrosis factor alpha (TNF-␣) and IL-6 even when the activity of the reference LPS was completely suppressed. A characteristic of B. cepacia LPS is that it has selectively weak interleukin-1␤ (IL-1␤)-inducing activity while activity to induce TNF-␣ and IL-6 has been shown to be as strong as that of the reference LPS. Remarkably, PmxB augmented the IL-1␤-inducing activity of B. cepacia LPS to the level of that of the reference LPS and, in contrast, completely suppressed the strong activity of the reference LPS. Using PmxB-immobilized beads, the adsorbances of these LPSs to the beads were compared, and it was found that B. cepacia LPS bound to PmxB with a high affinity similar to that of the reference LPS. These results indicate an unusual interaction of B. cepacia LPS with PmxB whereby B. cepacia LPS not only allows the binding of PmxB with high affinity, even though it contains Ara4N, but also suffers no suppressive effect of PmxB on its activity. Moreover, a remarkable increase in its IL-1␤-inducing activity was also observed.

show abstract

Polymyxin B Prevents Lipopolysaccharide-Induced Release of Tumor Necrosis Factor- from Alveolar Macrophages

Cited by 80 publications

References 22 publications

Exopolysaccharides from Burkholderia cenocepacia Inhibit Neutrophil Chemotaxis and Scavenge Reactive Oxygen Species

Exopolysaccharides from Burkholderia cenocepacia Inhibit Neutrophil Chemotaxis and Scavenge Reactive Oxygen Species

Lipomannans, But Not Lipoarabinomannans, Purified fromMycobacterium chelonaeandMycobacterium kansasiiInduce TNF-α and IL-8 Secretion by a CD14-Toll-Like Receptor 2-Dependent Mechanism

Unusual Interaction of a Lipopolysaccharide Isolated fromBurkholderia cepaciawith Polymyxin B

Contact Info

Product

Resources

About