Related Experiment Videos
A comparison of the effects of intact and deacylated lipopolysaccharide on human polymorphonuclear leukocytes
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Abstract:
Enzymatic deacylation of LPS markedly reduces its activity in the dermal Shwartzman reaction. Inasmuch as polymorphonuclear leukocytes (PMN) are involved in the genesis of tissue injury in Shwartzman reactions, we have investigated the effects of deacylated LPS (dLPS) on PMN. Compared to LPS, dLPS was ineffectual as a stimulus of both PMN adherence and release of secondary granule enzymes, and dLPS inhibited specific LPS-induced adherence. Neither LPS nor dLPS caused release of the primary granule enzymes, myeloperoxidase, and elastase. Unlike LPS, dLPS failed to prime PMN for superoxide release when a second stimulus (FMLP, 10(-6) M was given. The mechanism of the LPS induced increase in PMN adherence was investigated, and we found that LPS significantly increased the amount of the adhesive glycoprotein CD11b on the surface of the PMN. dLPS had no effect on CD11b expression. Our results suggest that enzymatic deacylation of LPS profoundly alters its ability to stimulate PMN and deacylation of LPS by inflammatory cells in vivo might be an important mechanism limiting the toxic effects of LPS.
Insights
Enzymatic deacylation of lipopolysaccharide (LPS) significantly reduces its inflammatory activity. Deacylated LPS (dLPS) does not stimulate polymorphonuclear leukocytes (PMN), suggesting a natural mechanism to limit LPS toxicity.
Area of Science:
- Immunology
- Biochemistry
Background:
- Lipopolysaccharide (LPS) is a potent endotoxin that triggers inflammatory responses.
- Polymorphonuclear leukocytes (PMN) play a key role in LPS-induced tissue injury during the Shwartzman reaction.
Purpose of the Study:
- To investigate the effects of enzymatically deacylated LPS (dLPS) on PMN function.
- To elucidate the mechanism by which LPS stimulates PMN adherence.
Main Methods:
- Comparison of LPS and dLPS effects on PMN adherence and enzyme release.
- Assessment of PMN priming for superoxide release.
- Analysis of CD11b surface expression on PMN.
Main Results:
- dLPS was ineffective in stimulating PMN adherence and secondary granule enzyme release.
- dLPS inhibited LPS-induced PMN adherence and failed to prime PMN for superoxide release.
- LPS increased PMN surface CD11b expression, while dLPS had no effect.
Conclusions:
- Enzymatic deacylation of LPS significantly alters its ability to stimulate PMN.
- In vivo deacylation of LPS by inflammatory cells may limit its toxic effects.