Relationship between tumor necrosis factor-alpha and neutrophils in endotoxin-induced liver injury

Hewett, James A.; Jean, Paul A.; Kunkel, S. L.; Roth, Robert A.

doi:10.1152/ajpgi.1993.265.6.g1011

Cited by 93 publications

(78 citation statements)

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“…Granulocytes infiltrate the liver in response to low dose LPS challenge and play a critical role in low dose LPS-induced shock/ liver injury (13)(14)(15)(16)(17). Although by 8 h after low dose LPS challenge, granulocytes infiltrated the liver, the number of liver granulocytes was slightly higher in LFA-1 Ϫ/Ϫ mice than in heterozygous littermates.…”

Section: Discussionmentioning

confidence: 98%

“…Interactions of LFA-1/ICAMs promote firm adhesion of leukocytes to vascular endothelium as the initiating event for transmigration of leukocytes into sites of inflammation (11). Infiltration of granulocytes into the liver has been suggested as crucial event in low dose LPS-induced liver damage (13)(14)(15). Although the ␤ 2 integrin family member, Mac-1 (CD11b/CD18), has been suggested to participate in low dose LPS-induced shock/liver injury (16,17), the role of LFA-1 in low dose LPS-induced shock/liver injury remains elusive.…”

Section: Increased Resistance Of Lfa-1-deficient Mice Tomentioning

confidence: 99%

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Increased Resistance of LFA-1-Deficient Mice to Lipopolysaccharide-Induced Shock/Liver Injury in the Presence of TNF-α and IL-12 Is Mediated by IL-10: A Novel Role for LFA-1 in the Regulation of the Proinflammatory and Anti-Inflammatory Cytokine Balance

Emoto¹,

Emoto²,

Brinkmann

et al. 2003

The Journal of Immunology

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Challenge with low doses of LPS together with d-galactosamine causes severe liver injury, resulting in lethal shock (low dose LPS-induced shock). We examined the role of LFA-1 in low dose LPS-induced shock. LFA-1−/− mice were more resistant to low dose LPS-induced shock/liver injury than their heterozygous littermates, although serum levels of TNF-α and IL-12 were higher in these mice. C57BL/6 mice were not rescued from lethal effects of LPS by depletion of NK1+ cells, granulocytes, or macrophages, and susceptibility of NKT cell-deficient mice was comparable to that of controls. High numbers of platelets were detected in the liver of LFA-1+/− mice after low dose LPS challenge, whereas liver accumulation of platelets was only marginal in LFA-1−/− mice. Following low dose LPS challenge, serum levels of IL-10 were higher in LFA-1−/− mice than in LFA-1+/− mice, and susceptibility to low dose LPS-induced shock as well as platelet accumulation in the liver of LFA-1−/− mice were markedly increased by IL-10 neutralization. Serum levels of IL-10 in LFA-1+/− mice were only marginally affected by macrophage depletion. However, in LFA-1−/− mice macrophage depletion markedly reduced serum levels of IL-10, and as a corollary, susceptibility of LFA-1−/− mice to low dose LPS-induced shock was markedly elevated despite the fact that TNF-α levels were also diminished. We conclude that LFA-1 participates in LPS-induced lethal shock/liver injury by regulating IL-10 secretion from macrophages and that IL-10 plays a decisive role in resistance to shock/liver injury. Our data point to a novel role of LFA-1 in control of the proinflammatory/anti-inflammatory cytokine network.

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Section: Discussionmentioning

confidence: 98%

Section: Increased Resistance Of Lfa-1-deficient Mice Tomentioning

confidence: 99%

Increased Resistance of LFA-1-Deficient Mice to Lipopolysaccharide-Induced Shock/Liver Injury in the Presence of TNF-α and IL-12 Is Mediated by IL-10: A Novel Role for LFA-1 in the Regulation of the Proinflammatory and Anti-Inflammatory Cytokine Balance

Emoto¹,

Emoto²,

Brinkmann

et al. 2003

The Journal of Immunology

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“…Depending on dose and route of exposure, virtually any organ or tissue can be affected, and the hemodynamic and inflammatory responses can result in widespread tissue injury and multiple organ failure. Interventions that block PMNs or PMN-derived products protect from tissue injury and death in animal models of endotoxemia, thus illustrating the critical role that activated PMNs play in host pathogenic responses [4][5][6][7]. As discussed in detail below, PMNs exhibit a distinctive functional profile during endotoxemia.…”

Section: Introductionmentioning

confidence: 95%

Neutrophil migration during endotoxemia

Wagner

Roth

1999

Journal of Leukocyte Biology

177

125

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Endotoxemia is marked by a global activation of inflammatory responses, which can lead to shock, multiple organ failure, and the suppression of immune and wound healing processes. Neutrophils (PMNs) play a central role in some of these responses by accumulating in tissues and releasing reactive oxygen species and proteases that injure host structures. This review focuses on altered PMN migratory responses that occur during endotoxemia and their consequences in the development of pulmonary infection. The inflammatory mediators that might be responsible for these altered responses are discussed. The oxidant potential of PMNs is increased after exposure to endotoxin both in vitro and during clinical and experimental endotoxemia. However, other functions such as chemotaxis and phagocytosis are often depressed in these same cells. Endotoxin exposure renders PMNs hyperadhesive to endothelium. The sum of these effects produces activated inflammatory cells that are incapable of leaving the vasculature. As such, the endotoxic PMN is more likely to promote tissue injury from within microvascular beds than to clear pathogens from extravascular sites. Moreover, the functional characteristics of endotoxic PMNs are similar to those observed during trauma, burn injury, sepsis, surgery, and other inflammatory conditions. Accordingly, several clinical conditions might have a common effector in the activated, yet migratorially dysfunctional, PMN. Direct effects of endotoxin on PMNs as well as effects of endogenous mediators released during endotoxemia are discussed. Understanding PMN behavior during endotoxemia may provide basic and critical insights that can be applied to a number of inflammatory scenarios. J. Leukoc. Biol. 66: 10-24; 1999.

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“…Additionally, soluble factors synthesized and secreted by neutrophils suppress the production of proinflammatory cytokines (i.e., TNF-␣ and IL-6) by macrophages in culture (22). Elevated TNF-␣ mRNA expression in the livers and increased IL-1␤ and TNF-␣ levels in the sera of neutropenic rats or mice inoculated with endotoxin demonstrate the potential role of neutrophils in regulating proinflammatory cytokine production by macrophages in vivo (6,(23)(24)(25). Elevated serum levels of IL-1␤, IL-6 and TNF-␣ in neutropenic patients indicates the clinical relevance of these observations (26).…”

mentioning

confidence: 99%

Neutrophils Sequestered in the Liver Suppress the Proinflammatory Response of Kupffer Cells to Systemic Bacterial Infection

Holub

Cheng

Mott

et al. 2009

The Journal of Immunology

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The liver plays a major role in clearing bacteria from the bloodstream. Rapid clearance is primarily the function of fixed tissue macrophages (Kupffer cells) that line the hepatic sinusoids. Although Kupffer cells play a critical role in blood clearance, the actual elimination of the bulk of bacteria taken up by the liver depends upon the accumulation of bactericidal neutrophils. Subsequent experiments demonstrating neutrophils inside Kupffer cells derived from infected animals prompted our speculation that neutrophils modulate the proinflammatory response of Kupffer cells to bacteria cleared from the bloodstream. Indeed, we report here that neutrophils accumulated in the liver sinusoids suppress cytokine and chemokine mRNA expression and protein production by Kupffer cells. Using listeriosis in mice as an experimental model, we found that IL-1β, IL-6, IL-10, IL-12, TNF-α, MIP-1α, keratinocyte-derived chemokine, and MCP-1 mRNA levels were ≥10-fold more in the livers of Listeria-infected, relative to noninfected control, mice at 0.5–2 h after i.v. infection. Most message levels were sharply diminished thereafter, correlating inversely with increased neutrophil sequestration. Relative to intact animals, mice rendered neutrophil deficient exhibited marked increases in cytokine/chemokine mRNA expression and protein production in the liver subsequent to infection. Moreover, purified Kupffer cells derived from infected, neutrophil-depleted mice produced significantly more IL-6, IL-10, IL-12, TNF-α, keratinocyte-derived chemokine, and MCP-1 in culture. These findings document the critical role of neutrophils in moderating the proinflammatory response of Kupffer cells to bacteria taken up by the liver.

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Relationship between tumor necrosis factor-alpha and neutrophils in endotoxin-induced liver injury

Cited by 93 publications

References 0 publications

Increased Resistance of LFA-1-Deficient Mice to Lipopolysaccharide-Induced Shock/Liver Injury in the Presence of TNF-α and IL-12 Is Mediated by IL-10: A Novel Role for LFA-1 in the Regulation of the Proinflammatory and Anti-Inflammatory Cytokine Balance

Increased Resistance of LFA-1-Deficient Mice to Lipopolysaccharide-Induced Shock/Liver Injury in the Presence of TNF-α and IL-12 Is Mediated by IL-10: A Novel Role for LFA-1 in the Regulation of the Proinflammatory and Anti-Inflammatory Cytokine Balance

Neutrophil migration during endotoxemia

Neutrophils Sequestered in the Liver Suppress the Proinflammatory Response of Kupffer Cells to Systemic Bacterial Infection

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