β2-Microglobulin knockout mice treated with anti-asialoGM1 exhibit improved hemodynamics and cardiac contractile function during acute intra-abdominal sepsis

Tao, Weike; Sherwood, Edward R.

doi:10.1152/ajpregu.00470.2003

Cited by 16 publications

(17 citation statements)

References 41 publications

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“…The presence of severe metabolic acidosis indicates that a state of tissue hypoperfusion exists in wild-type mice after CLP. This is consistent with our previous reports showing that the ultimate mechanism of mortality in wild-type mice after CLP is cardiovascular collapse and shock (25)(26)(27). Treatment of wild-type mice with imipenem did not improve CLP-induced hypothermia and metabolic acidosis, which indicates that systemic infection is not the underlying cause of these alterations.…”

Section: Discussionsupporting

confidence: 92%

Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β₂-microgloblin knockout mice

Enoh

Chen

Varma

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Our previous studies showed that beta(2)-microglobulin knockout mice treated with anti-asialoGM1 (beta2MKO/alphaAsGM1 mice) are resistant to injury caused by cecal ligation and puncture (CLP). However, CLP-induced injury is complex. Potential mechanisms of injury include systemic infection, cecal ischemia, and translocation of bacterial toxins such as endotoxin and superantigens. Currently, it is unclear which of these mechanisms of injury contributes to mortality in wild-type mice and whether beta2MKO/alphaAsGM1 mice are resistant to any particular mechanisms of injury. In the present study, we hypothesized that systemic infection is the major cause of injury after CLP in wild-type mice and that beta2MKO/alphaAsGM1 mice are resistant to infection-induced injury. To test this hypothesis, wild-type and beta2MKO/alphaAsGM1 mice were treated with the broad-spectrum antibiotic imipenem immediately after CLP to decrease the impact of systemic infection in our model. Treatment of wild-type and beta2MKO/alphaAsGM1 mice with imipenem decreased bacterial counts by at least two orders of magnitude. However, all wild-type mice, whether treated with saline or imipenem, died by 42 h after CLP and had significant hypothermia, metabolic acidosis, and high plasma concentrations of the cytokines interleukin-6, macrophage inflammatory protein-2, and keratinocyte-derived chemokine. beta2MKO/alphaAsGM1 mice showed 40% long-term survival, which was increased to 90% by imipenem treatment. beta2MKO/alphaAsGM1 mice had less hypothermia, decreased metabolic acidosis, and lower cytokine concentrations at 18 h after CLP compared with wild-type mice. These results suggest that infection is not the major cause of mortality for wild-type mice in our model of CLP. Other mechanisms of injury such as cecal ischemia or translocation of microbial toxins may be more important. beta2MKO/alphaAsGM1 mice appear resistant to these early, non-infection-related causes of CLP-induced injury but showed delayed mortality associated with bacterial dissemination, which was ablated by treatment with imipenem.

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Section: Discussionsupporting

confidence: 92%

Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β₂-microgloblin knockout mice

Enoh

Chen

Varma

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Our studies using ␤ 2 -microglobulin knockout mice show decreased systemic inflammation, less cardiovascular dysfunction, and improved survival after CLP, compared with wildtype controls (11)(12)(13). However, ␤ 2 -microglobulin knockout mice have multiple immunological defects in addition to NKT cell deficiency (14,15).…”

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confidence: 64%

NK but Not CD1-Restricted NKT Cells Facilitate Systemic Inflammation during Polymicrobial Intra-Abdominal Sepsis

Etogo

Nunez

Chen

et al. 2008

The Journal of Immunology

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Evidence suggests that NK and NKT cells contribute to inflammation and mortality during septic shock caused by cecal ligation and puncture (CLP). However, the specific contributions of these cell types to the pathogenesis of CLP-induced septic shock have not been fully defined. The goal of the present study was to determine the mechanisms by which NK and NKT cells mediate the host response to CLP. Control, NK cell-deficient, and NKT cell-deficient mice underwent CLP. Survival, cytokine production, and bacterial clearance were measured. NK cell trafficking and interaction with myeloid cells was also studied. Results show that mice treated with anti-asialoGM1 (NK cell deficient) or anti-NK1.1 (NK/NKT cell deficient) show less systemic inflammation and have improved survival compared with IgG-treated controls. CD1 knockout mice (NKT cell deficient) did not demonstrate decreased cytokine production or improved survival compared with wild type mice. Trafficking studies show migration of NK cells from blood and spleen into the inflamed peritoneal cavity where they appear to facilitate the activation of peritoneal macrophages (F4-80+GR-1−) and F4-80+Gr-1+ myeloid cells. These findings indicate that NK but not CD1-restricted NKT cells contribute to acute CLP-induced inflammation. NK cells appear to mediate their proinflammatory functions during septic shock, in part, by migration into the peritoneal cavity and amplification of the proinflammatory activities of specific myeloid cell populations. These findings provide new insights into the mechanisms used by NK cells to facilitate acute inflammation during septic shock.

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“…We previously analyzed the left ventricular pressure-volume relationship with a conductance catheter in mice after sepsis induced by cecal ligation and puncture (8,9), and demonstrated a distinct pattern of myocardial depression associated with sepsis despite a seemingly normal cardiac output. Variables obtained with this model allowed us to separate myocardial depression from the global hemodynamic response.…”

Section: Introductionmentioning

confidence: 99%

Murine in Vivo Myocardial Contractile Dysfunction After Burn Injury Is Exacerbated by Pneumonia Sepsis

Tao¹,

Maass²,

Horton³

2005

Shock

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We evaluated hemodynamic and cardiac contractile dysfunction in a murine model of 40% contact burn complicated by Streptococcus pneumoniae (1 x 10(5) CFU) sepsis. Male, 9- to 10-week-old C57/BL6 mice were divided into the following groups: sham burn, sham sepsis; 24 h after burn alone; 24 h after sepsis alone; 7 days after burn alone; and 7 days after burn followed by pneumonia sepsis. Hemodynamic and cardiac contractile function was assessed with carotid artery cannulation and left ventricular pressure-volume analysis. At 24 h after burn, there were significant decreases in all load-insensitive contractility variables including the end-systolic pressure volume relationship, preload-recruitable stroke work, and maximum elastance, but there were no changes in global hemodynamics. Twenty-four hours after sepsis, there was similar cardiac contractile dysfunction, along with a decrease in cardiac output, but mean arterial pressure was maintained with an increase in systemic vascular resistance. Late burn (7 days) was associated with a recovery of all contractility variables except the end-systolic pressure volume relationship. However, sepsis induced during the late burn period was associated with a significant decrease in heart rate and cardiac output, but mean arterial pressure was still maintained with increased systemic vascular resistance. With burn complicated by sepsis, all cardiac contractility variables showed profound contractile dysfunction. Our data indicate that burn complicated by sepsis is associated with more pronounced cardiac contractile dysfunction than burn alone or sepsis alone.

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β2-Microglobulin knockout mice treated with anti-asialoGM1 exhibit improved hemodynamics and cardiac contractile function during acute intra-abdominal sepsis

Cited by 16 publications

References 41 publications

Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β₂-microgloblin knockout mice

Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β₂-microgloblin knockout mice

NK but Not CD1-Restricted NKT Cells Facilitate Systemic Inflammation during Polymicrobial Intra-Abdominal Sepsis

Murine in Vivo Myocardial Contractile Dysfunction After Burn Injury Is Exacerbated by Pneumonia Sepsis

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β2-Microglobulin knockout mice treated with anti-asialoGM1 exhibit improved hemodynamics and cardiac contractile function during acute intra-abdominal sepsis

Cited by 16 publications

References 41 publications

Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β2-microgloblin knockout mice

Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β2-microgloblin knockout mice

NK but Not CD1-Restricted NKT Cells Facilitate Systemic Inflammation during Polymicrobial Intra-Abdominal Sepsis

Murine in Vivo Myocardial Contractile Dysfunction After Burn Injury Is Exacerbated by Pneumonia Sepsis

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Resources

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Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β₂-microgloblin knockout mice

Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β₂-microgloblin knockout mice