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Induction of proinflammatory responses in human monocytes by particulate and soluble forms of lipopolysaccharide
1Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City 66160, USA.
Abstract:
Lipopolysaccharide (LPS), a major constituent of the outer membrane of Gram-negative bacteria, is thought to be chiefly responsible for induction by these organisms of Gram-negative septic shock, an often fatal complication of Gram-negative septicemia. Accordingly, monocytes and macrophages, which are believed to be the primary cellular targets of LPS, have been shown to mount vigorous proinflammatory responses to highly purified, soluble LPS. Relatively less is known, however, about the ability of these cells to respond to native, insoluble forms of LPS, such as those represented by intact Gram-negative bacterial particles. Furthermore, the intact microbe would be expected to exhibit additional non-LPS components that are capable of stimulating proinflammatory responses, and the relative roles of these components and LPS in stimulating proinflammatory responses have not, to date, been fully defined. Therefore, experiments have been conducted to assess stimulation of human monocytes by highly purified, soluble LPS as well as by particulate forms of LPS, including Gram-negative bacterial particles and LPS-coated latex beads. As indicated by induction of procoagulant activity and production of tumor necrosis factor, LPS appears to be the Gram-negative bacterial component of primary importance for induction of monocytic proinflammatory responses. Furthermore, the presentation of LPS associated with the bacterial surface is also capable of eliciting such responses, albeit with less potency than that observed for soluble LPS. At least part of this reduction in potency appears attributable to the particulate nature of bacterium-bound LPS, since a reduction in potency is similarly observed for soluble LPS coated onto latex beads.
Insights
Lipopolysaccharide (LPS) from Gram-negative bacteria strongly activates monocytes. While both soluble and surface-bound LPS induce inflammatory responses, soluble forms are more potent than bacterial particles or LPS-coated beads.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Lipopolysaccharide (LPS) is a key component of Gram-negative bacteria, implicated in septic shock.
- Monocytes and macrophages are primary targets of LPS, mounting proinflammatory responses.
- The role of native, insoluble LPS forms and non-LPS bacterial components in immune stimulation is less understood.
Purpose of the Study:
- To investigate human monocyte stimulation by soluble and particulate forms of LPS.
- To compare the proinflammatory responses induced by intact bacteria, LPS-coated beads, and soluble LPS.
- To define the relative importance of LPS and other bacterial components in monocyte activation.
Main Methods:
- Assessed human monocyte stimulation using purified soluble LPS.
- Utilized particulate LPS forms, including whole Gram-negative bacteria and LPS-coated latex beads.
- Measured procoagulant activity and tumor necrosis factor production as indicators of proinflammatory response.
Main Results:
- LPS is the primary Gram-negative bacterial component inducing monocytic proinflammatory responses, evidenced by procoagulant activity and TNF production.
- Surface-bound LPS on intact bacteria elicits inflammatory responses, but with reduced potency compared to soluble LPS.
- The particulate nature of LPS, whether on bacteria or beads, contributes to reduced stimulation potency.
Conclusions:
- Lipopolysaccharide is the dominant factor driving Gram-negative bacteria-induced monocytic inflammation.
- Soluble LPS is a more potent stimulus than LPS presented in particulate forms.
- Bacterial surface components and LPS's physical presentation influence the magnitude of monocyte activation.