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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemorrhagic shock/reperfusion (HS/R) followed by sepsis triggers systemic microcirculatory disturbances that may induce multiple organ failure. The present study evaluated the effects of HS/R and cecal ligation and puncture, followed by necrotic cecal resection/peritoneal lavage (REL) on leukocyte-endothelium interactions at the mesentery. Eighty-one anesthetized Wistar rats (200-250 g) were randomly assigned to a first injury: (1) control-HS-no hemorrhagic shock/no reperfusion group, (2) HS/blood-HS/R with 25% shed blood, and (3) HS/blood + LR-HS/R with 25% of the shed blood + lactated Ringer's solution, 3x shed blood volume. Twenty-four hours post-HS/R, animals were submitted to cecal ligation and puncture and, 24 h thereafter, to REL. Leukocyte-endothelium interactions were assessed by intravital microscopy and intercellular adhesion molecule (ICAM) 1 and P-selectin expression by immunohistochemistry. Lungs were observed for ICAM-1 expression and neutrophil infiltration. Single and double injury induced significant increases in rolling (approximately 2-fold), adherent (approximately 5-fold), and migrated leukocytes (approximately 7-fold); ICAM-1 expression (approximately 1/2-fold), and P-selectin expression (approximately 1/2-fold) at the mesentery compared with control-HS group. REL normalized leukocyte-endothelium interactions at the mesentery in single-injured animals. However, in double-injured rats, adherence and migration of leukocytes decreased but did not normalize. Similar results were observed on ICAM-1 expression and neutrophil infiltration in the lungs from these animals. In conclusion, the current in vivo observation of the mesenteric microcirculation after a double injury followed by REL is a suitable model for the systematic evaluation of the inflammatory reaction at local and distant sites. In addition, data presented herein emphasized the importance of surgical removal of the septic focus in controlling the otherwise lethal sepsis-induced multiple organ dysfunction syndrome.
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PMID:Leukocyte-endothelium interactions after hemorrhagic shock/reperfusion and cecal ligation/puncture: an intravital microscopic study in rat mesentery. 1687 27

The lipopolysaccharide (LPS)-receptor complex, CD14/toll-like receptor 4, is known to play a role in the immune responses during sepsis. Excessive inflammation and tumor necrosis factor (TNF)-alpha synthesis have been reported to cause morbidity and mortality in endotoxemia and sepsis. Cell-to-cell interaction through the engagement between intercellular adhesion molecule 1, B7.1, and CD40 on monocytes and their ligands on T cells has been suggested to play a role in the inflammatory response such as TNF-alpha and interleukin 10 production. Nicotine, with the stimulation of the nicotinic acetylcholine receptor alpha7 subunit (alpha7-nAChR), has now become the focus of attention because of its anti-inflammatory effects. However, little is known about the mechanism of the inhibitory effects induced by nicotine on the LPS-induced immune responses. In the present study, we found that nicotine suppressed the expression of CD14, toll-like receptor 4, intercellular adhesion molecule 1, B7.1, and CD40 on monocytes and the production of TNF-alpha, but not interleukin 10, in human peripheral blood mononuclear cells in the presence of LPS. The actions of nicotine were reversed by a nonselective and a selective alpha7-nAChR antagonist, mecamylamine and alpha-bungarotoxin, respectively. Therefore, nicotine might inhibit the LPS receptor complex expression via alpha7-nAChR, thus leading to a decrease in the adhesion molecule expression and TNF-alpha production. Moreover, we demonstrated that a nuclear factor-kappaB and a p38 mitogen-activated protein kinase inhibitor mimicked the actions of nicotine in the presence of LPS. These results suggested that the nuclear factor-kappaB and p38 mitogen-activated protein kinase might be involved in the actions of nicotine.
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PMID:Stimulation of alpha7 nicotinic acetylcholine receptor inhibits CD14 and the toll-like receptor 4 expression in human monocytes. 1698 Aug 82

This study investigated the effects of fish oil (FO) diet on plasma intercellular adhesion molecule 1 (ICAM-1) levels and leucocyte integrin expression in polymicrobial sepsis. Mice were randomly assigned to a control group and an FO group. The control group was fed a medium-fat diet containing soyabean oil, whereas in the FO group, 70 % of the soyabean oil was replaced by FO for 3 weeks. After that, sepsis was induced by caecal ligation and puncture (CLP) in the experimental groups and mice were killed at 0, 6, 12 and 24 h, respectively, after CLP. Results showed that compared with the control group, plasma ICAM-1 levels were higher in the FO group 6 h after CLP. Intra-lymphocyte interferon-gamma expression in the FO group was lower, whereas IL-4 expression was higher than in the control group 12 and 24 h after CLP. The expression of leucocyte integrin was significantly higher in the FO group 12 and 24 h after CLP. The FO group had higher IL-6 levels at 12 h in the lungs, at 6 and 12 h in the kidneys, and at 6, 12 and 24 h in the intestines after CLP. The survival rate did not differ between the two groups after CLP. The present findings suggest that pretreatment with an FO diet enhances adhesion molecule and inflammatory cytokine expressions during sepsis, which might aggravate the inflammatory reaction and increase neutrophil infiltration into tissues. In addition, FO diet promotes the Th2-type response and suppresses cellular immune response in polymicrobial sepsis.
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PMID:Dietary fish oil enhances adhesion molecule and interleukin-6 expression in mice with polymicrobial sepsis. 1709 73

Endosialidase (endo-N-acetylneuraminidase) is a tailspike enzyme of bacteriophages specific for human pathogenic Escherichia coli K1, which specifically recognizes and degrades polySia (polysialic acid). polySia is also a polysaccharide of the capsules of other meningitis- and sepsis-causing bacteria, and a post-translational modification of the NCAM (neural cell-adhesion molecule). We have cloned and sequenced three spontaneously mutated endosialidases of the PK1A bacteriophage and one of the PK1E bacteriophage which display lost or residual enzyme activity but retain the binding activity to polySia. Single to triple amino acid substitutions were identified, and back-mutation constructs indicated that single substitutions accounted for only partial reduction of enzymic activity. A homology-based structural model of endosialidase revealed that all substituted amino acid residues localize to the active site of the enzyme. The results reveal the importance of non-catalytic amino acid residues for the enzymatic activity. The results reveal the molecular background for the dissociation of the polySia binding and cleaving activities of endosialidase and for the evolvement of 'host range' mutants of E. coli K1 bacteriophages.
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PMID:Identification of amino acid residues at the active site of endosialidase that dissociate the polysialic acid binding and cleaving activities in Escherichia coli K1 bacteriophages. 1739 21

Sepsis is one of the most important risk factors in acute respiratory distress syndrome (ARDS). beta-Glucan is a potent reticuloendothelial modulating agent, the immunobiological activity of which is mediated in part by an increase in the number and function of macrophages. In this study, we investigated the putative protective role of beta-glucan against sepsis-induced lung injury. Sepsis was induced by cecal ligation and puncture (CLP) in Wistar rats. The control group received saline, and the treatment groups received beta-glucan or beta-glucan + beta-1,3-D-glucanase. Five hours thereafter, plasma tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, and IL-6 levels were determined. Presence of lung injury was determined via lung tissue myeloperoxidase (MPO) activity, intercellular adhesion molecule (ICAM) 1 levels, and histopathological examination at 18 h after CLP. In a separate set of experiments, survival was monitored for 7 days after CLP. beta-Glucan treatment led to a significant increase in survival rate (63% in glucan-treated rats vs 38% in saline-treated rats). Administration of the beta-glucan inhibitor abrogated beta-glucan's survival benefit (50%). After CLP, plasma TNF-alpha, IL-1beta, and IL-6 concentrations were increased in control animals. When beta-glucan was administered, it completely blocked the elevation of TNF-alpha, IL-1beta, and IL-6. Administration of beta-1,3-D-glucanase suppressed glucan-induced decrease in cytokines. Animals treated with beta-glucan showed a significant reduction in lung injury score, a marked decrease in ICAM-1 expression, and a significant decrease in MPO levels. In contrast, beta-1,3-D-glucanase caused a significantly increased MPO and ICAM-1 levels in the lung. These data reveal that beta-glucan treatment improved the course of CLP-induced peritonitis and attenuated the lung injury. Administration of beta-glucanase inhibited the beta-glucan activity and resulted in enhanced lung injury.
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PMID:Beta-glucan attenuates inflammatory cytokine release and prevents acute lung injury in an experimental model of sepsis. 1741 22

Tumor necrosis factor (TNF) is critically involved in biological responses against various insults. TNF excessively produced by monocytes or macrophages activates endothelial cells and neutrophils, thereby inducing endothelial cell injury. Endothelial cells are capable of inhibiting TNF production by producing prostaglandins that inhibit TNF production. Sensory neurons play an important role in promotion of the endothelial production of prostaglandins by releasing calcitonin gene-related peptide. Neutrophils activated by TNF release a huge amount of neutrophil elastase that is capable of decreasing endothelial prostaglandin production. Consequently, TNF production is enhanced, leading to the development of multi-organ failure in sepsis. E-selectin, an endothelial leukocyte adhesion molecule, is released from the endothelial cell membrane by the action of TNF and exists as soluble E-selectin in plasma. The detection of increases in plasma levels of soluble E-selectin in patients with systemic inflammatory response syndrome predicts the imminent onset of acute respiratory syndrome. Early detection of increases in plasma levels of soluble E selectin by a rapid assay system, developed by the authors, enables early effective treatment of patients with sepsis.
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PMID:[Role of endothelial dysfunction in the development of severe sepsis--the pathomechanism, evaluation by laboratory tests and new therapeutic strategies]. 1744 73

Increased expression of adhesion molecules by activated endothelium is a critical feature of vascular inflammation associated with the several diseases such as endotoxin shock and sepsis/septic shock. Our data demonstrated complement regulatory protein C1 inhibitor (C1INH) prevents endothelial cell injury. We hypothesized that C1INH has the ability of an anti-endothelial activation associated with suppression of expression of adhesion molecule(s). C1INH blocked leukocyte adhesion to endothelial cell monolayer in both static assay and flow conditions. In inflammatory condition, C1INH reduced vascular cell adhesion molecule (VCAM-1) expression associated with its cytoplasmic mRNA destabilization and nuclear transcription level. Studies exploring the underlying mechanism of C1INH-mediated suppression in VCAM-1 expression were related to reduction of NF-kappaB activation and nuclear translocation in an IkappaBalpha-dependent manner. The inhibitory effects were associated with reduction of inhibitor IkappaB kinase activity and stabilization of the NF-kappaB inhibitor IkappaB. These findings indicate a novel role for C1INH in inhibition of vascular endothelial activation. These observations could provide the basis for new therapeutic application of C1INH to target inflammatory processes in different pathologic situations.
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PMID:Suppression of complement regulatory protein C1 inhibitor in vascular endothelial activation by inhibiting vascular cell adhesion molecule-1 action. 1752 9

Adhesion molecules may play a role in the evolution and severity of neonatal sepsis. The purposes of this study were to determine whether serum soluble intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, L-selectin, and P-selectin levels are useful tools in the diagnosis of proven sepsis in newborn infants, and whether their levels are related to the clinical severity of the disease. A cohort of 25 consecutive newborns meeting criteria for clinical sepsis, 10 hemoculture-negative (HC - ) and 15 hemoculture-positive (HC + ), were prospectively followed and compared with 12 healthy newborns (six </= 38 weeks of gestational age and six >/= 39 weeks). Serum soluble (s)ICAM-1, sVCAM-1, sL-selectin, and sP-selectin concentrations were measured at the time of the septic workup, then followed by up to three determinations in each newborn every third day. The Score for Neonatal Acute Physiology (SNAP)-II severity was assessed at the moment of highest clinical severity of the disease. At the beginning of sepsis, sICAM-1 levels increased in both groups, being higher in HC + sepsis than in HC - ; sVCAM-1 only increased slightly in HC + sepsis. Soluble ICAM-1 levels were independently related to group of sepsis, and not to days of life. The best initial sICAM-1 cutoff level for diagnosing HC + neonatal sepsis was 274 microg/L. The highest sICAM-1 levels were positively correlated with SNAP-II scores. Soluble L-selectin and sP-selectin did not change. Soluble ICAM-1 levels increased in HC - and HC + sepsis, but concentrations > 274 microg/L suggest HC + sepsis. These levels were related to the clinical severity of the disease. Soluble VCAM-1 levels increased only slightly in HC + sepsis. Soluble L-selectin and sP-selectin did not change.
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PMID:Serum soluble ICAM-1, VCAM-1, L-selectin, and P-selectin levels as markers of infection and their relation to clinical severity in neonatal sepsis. 1756 56

Leukocyte adhesion deficiency type I (LAD I) is characterized by recurrent and fatal bacterial infections, and caused by the mutation of the CD18 gene. A 9-month-old infant whose umbilical cord separated at day 10 of life had sepsis, complicated otitis media and neutrophilia. Molecular analysis showed homozygous intron 7 (+1) g > a in the CD18 gene, resulting in three splicing transcriptions that inserted 64, 298 (5' end of intron 7), and 1157 (whole intron 7) nucleotides into the 300th amino acid of Ile and stopped at the 326th (inserted 64 and 1157 nucleotides) and the 344th (inserted 64 nucleotides), respectively. The two truncated mutations lost cysteine-rich, transmembrane, and cytoplasma domains. Increased susceptibility to infections correlated to polymorphonuclear cell dysfunction, including absent expression of adhesion molecule (CD11b/CD18), impaired chemotaxis, and decreased phagocytosis. Both his heterozygous parents revealed non-random skewing only to the wild type. The skewing pattern and severe phenotype make stem cell transplantation an optimal option.
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PMID:Neutrophil function and molecular analysis in severe leukocyte adhesion deficiency type I without separation delay of the umbilical cord. 1765 79

Recent studies suggest that exogenously administered CO is beneficial for the resolution of acute inflammation. In this study, we assessed the role of CO liberated from a systemically administered tricarbonyldichlororuthenium-(II)-dimer (CORM-2) on modulation of liver inflammation during sepsis. Polymicrobial sepsis in mice was induced by cecal ligation and perforation (CLP). CORM-2 (8 mg/kg iv) was administered immediately after CLP induction, and neutrophil [polymorphonuclear leukocyte (PMN)] tissue accumulation, activation of transcription factor, NF-kappaB, and changes in adhesion molecule ICAM-1 expression (inflammation-relevant markers) were assessed in murine liver 24 h later. In addition, the effects and potential mechanisms of CORM-2-released CO in modulation of vascular endothelial cell proinflammatory responses were assessed in vitro. To this end, human umbilical vein endothelial cells (HUVEC) were stimulated with LPS (1 microg/ml) in the presence or absence of CORM-2 (10-100 microM) and production of intracellular reactive oxygen species (ROS), (DHR123 oxidation) and NO (DAF-FM nitrosation) and subsequent activation of NF-kappaB were assessed 4 h later. In parallel, expression of ICAM-1 and inducible NO synthase (iNOS) proteins along with PMN adhesion to LPS-challenged HUVEC were also assessed. Induction of CLP resulted in increased PMN accumulation, ICAM-1 expression, and activation of NF-kappaB in the liver of septic mice. These effects were significantly attenuated by systemic administration of CORM-2. In in vitro experiments, CORM-2-released CO attenuated LPS-induced production of ROS and NO, activation of NF-kappaB, increase in ICAM-1 and iNOS protein expression and PMN adhesion to LPS-stimulated HUVEC. Taken together, these findings indicate that CO released from systemically administered CORM-2 provides anti-inflammatory effects by interfering with NF-kappaB activation and subsequent downregulation of proadhesive vascular endothelial cell phenotype in the liver of septic mice.
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PMID:Carbon monoxide liberated from carbon monoxide-releasing molecule CORM-2 attenuates inflammation in the liver of septic mice. 1799 8


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