Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various cell types, including endothelial cells, can synthesize nitric oxide (NO). Three different isoforms of NO synthase have been characterized, purified and cloned. Isozyme I is present in neuronal cells of the brain (where NO may mediate synaptic plasticity), in peripheral non-adrenergic non-cholinergic (NANC) neurons (where NO acts as an atypical neurotransmitter relaxing vascular and non-vascular smooth muscle), and in various specialized epithelial cells. Macrophages can be induced with bacterial endotoxin and/or cytokines to express isozyme II. The high concentrations of NO produced by this isoform have cytostatic effects on parasitic microorganisms and tumour cells. A similar isozyme can be induced in the vascular wall (presumably in smooth muscle cells) in sepsis and during cytokine therapy. The large amounts of NO produced by this enzyme contribute to the symptoms of septic shock, such as vasodilatation and microvascular endothelial damage. Endothelial cells contain isoform III of NO synthase which seems to be unique for this cell type. Endothelium-derived NO is a physiologically significant vasodilator and inhibitor of platelet aggregation and adhesion. In addition, vascular NO can prevent leukocyte adhesion to the endothelium by interfering with the adhesion molecule CD11/CD18, and NO has also been shown to inhibit the proliferation of vascular smooth muscle cells. Hence, NO represents a protective factor against vascular damage and probably atherogenesis.
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PMID:Isoforms of nitric oxide synthase: functions in the cardiovascular system. 750 35

Interleukin-11 (IL-11), a newly-identified cytokine produced by stromal cells, elevates platelet counts in neonatal rats in vivo and synergizes in vitro with IL-3 in supporting murine megakaryocyte colony formation and stimulating hematopoietic stem cells. Megakaryocytopoiesis is also enhanced by other colony-stimulating factors (CSFs), including IL-3, IL-6, and Steel factor (SLF). Dysregulation of neonatal thrombopoiesis predisposes newborns to develop thrombocytopenia during sepsis, despite increased circulating pools of committed thrombopoietic progenitors in newborn cord blood compared with adult. We previously reported reduced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte-colony-stimulating factor (G-CSF), and IL-3 from stimulated cord mononuclear cells, but increased expression of SLF in human umbilical vein endothelial cells (HUVEC). Therefore, we hypothesized that IL-3, IL-6, and SLF might modulate megakaryocytopoiesis by inducing IL-11 expression, and newborns might express altered levels of IL-11 mRNA expression during activated conditions, contributing to the difference in circulating colony-forming unit-megakaryocyte (CFU-Meg) cord and adult blood. Phorbol myristate acetate (PMA) induced a twofold greater increase in IL-11 mRNA expression in neonatal fibroblasts (NFb) compared with adult fibroblasts (AFb), and a 3.6-fold greater increase in HUVEC than human adult aorta endothelial cells (HAEC) by Northern blot analysis. PMA also induced a threefold greater increase in IL-11 protein production in NFb than AFb. Physiologic agonists IL-1 alpha, transforming growth factor-beta 1 (TGF-beta 1), and TGF-beta 2 triggered upregulation of IL-11 mRNA expression in both NFb and AFb. However, IL-3, IL-6, PIXY321 (a GM-CSF-IL-3 fusion protein), and SLF failed to upregulate IL-11 mRNA expression from the basal level, while macrophage-colony stimulating factor (M-CSF) mRNA was significantly induced. These data suggest that the hematopoietic effect of IL-6, SLF, and IL-3 on megakaryocytopoiesis is probably not mediated by secondary IL-11 mRNA expression. Similarly, inflammatory agonists IL-1 beta, lipopolysaccharide (LPS), and tumor necrosis factor-alpha (TNF-alpha) alone did not upregulate IL-11 expression from the basal level in endothelial cells, whereas intracellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 were strongly induced. Minimal basal IL-11 expression was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in NFb, AFb, HUVEC and HAEC. The quantitative RT-PCR assay also verified that IL-1 beta and TNF-alpha-stimulated HUVEC and HAEC, and IL-3- and IL-6-stimulated NFb and AFb only expressed minimal levels of IL-11 mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of interleukin-11 protein and mRNA expression in neonatal and adult fibroblasts and endothelial cells. 752 67

Increased serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble endothelial leucocyte adhesion molecule-1 (sELAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were detected in Danish malaria patients infected with sequestering Plasmodium falciparum or non-sequestering P. vivax parasites, as well as in patients with sepsis or meningitis. Levels of soluble adhesion molecules remained elevated in the P. falciparum patients for several weeks after initiation of treatment. Plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 were higher in Gambian children with severe P. falciparum malaria than in children with mild malaria. Plasma levels of sVCAM-1 and sELAM-1 were significantly correlated. Plasma levels of sELAM-1 and sVCAM-1 may reflect endothelial inflammatory reactions and these reactions may be harmful for humans infected with malaria parasites.
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PMID:Increased plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 in patients with Plasmodium falciparum or P. vivax malaria and association with disease severity. 753 38

Microbicidal and cytocidal products of the respiratory burst and integrin adhesion molecule expression have been studied in monocytes from patients who received rHuGM-CSF during regeneration after high-dose chemotherapy. In this study, administration of rHuGM-CSF after high-dose chemotherapy significantly augmented the secretion of inducible products of the monocyte respiratory burst. Monocyte activation persisted for several weeks after the cessation of GM-CSF therapy. Under in vitro conditions that mimicked gram-negative (LPS) and gram-positive (opsonized Staphylococcus aureus) sepsis, the monocyte responded to such stimulation by exhibiting an enhanced release of hydrogen peroxide at both regeneration and several weeks later (P < 0.001). Similarly, GM-CSF administration significantly augmented the phenotypic expression of the beta 2-integrin adhesion molecules and allowed the leucocyte-specific selectin, LAM-1, and the beta 2-integrins to respond normally to inflammatory stimulation by LPS. We further present evidence that GM-CSF therapy restored the otherwise refractory status of monocytes to inflammatory stimulation that existed in those patients given chemotherapy alone. The restoration of monocyte responsiveness by GM-CSF following high-dose chemotherapy could be a potentially valuable and hitherto not described action of rHuGM-CSF on monocyte function. We conclude that administration of GM-CSF may have the potential for restoring as well as augmenting the anti-microbial and anti-tumour function of the monocyte after high-dose chemotherapy.
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PMID:Administration of rHuGM-CSF activates monocyte reactive oxygen species secretion and adhesion molecule expression in vivo in patients following high-dose chemotherapy. 754 Apr 15

During sepsis the infiltration of leukocytes plays a pivotal role in tissue damage. Induction of septic shock results in an early accumulation of polymorphonuclear leukocytes in the liver (after 3 hours), which is followed by an infiltration of mononuclear phagocytes (after 30 hours). Expression of adhesion molecules may contribute to the migration of leukocytes to the site of inflammation. Therefore, in the present study we determined the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) on hepatocytes, liver endothelial cells, and Kupffer cells after lipopolysaccharide (LPS) treatment of rats in vivo. Parenchymal cells showed no constitutive expression of VCAM-1 and the expression could not be upregulated by LPS treatment in vivo, whereas Kupffer and endothelial cells had a low basal expression of VCAM-1 and this expression was increased 40-fold by LPS treatment in vivo. All three cell types showed a basal expression of ICAM-1 and the expression on endothelial liver cells of untreated rats was two times higher than the expression on parenchymal and Kupffer cells. Stimulation with LPS increased the expression of ICAM-1 2.5 times per parenchymal cells and approximately 4 times for endothelial and Kupffer cells. It is concluded that the expression of adhesion molecules may contribute to the influx of leukocytes during septic shock and, therefore, play a role in tissue damage during septic shock.
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PMID:Vascular adhesion molecule-1 and intercellular adhesion molecule-1 expression on rat liver cells after lipopolysaccharide administration in vivo. 918 81

To evaluate the role of cellular activation markers and functional surface molecules in sepsis, specific immunophenotypes on peripheral blood leukocytes were studied in 40 subjects consisting of the following: (1) patients with septic shock; (2) patients with sepsis; (3) critically ill nonseptic patients; and (4) normal control subjects. These assays included phagocyte adhesion molecule CD11b expression, monocyte receptors HLA-DR and CD14, and lymphocyte activation markers IL-2R and HLA-DR. Patients with septic shock and sepsis had significantly increased neutrophil CD11b expression compared with normal subjects. Neutrophil HLA-DR expression did not significantly differ between groups. Monocytes from septic shock patients had significantly less HLA-DR expression than normal subjects and there was a trend toward a lower proportion of gated monocytes that expressed CD14 in septic shock patients. Septic shock patients had no significant increases in IL-2R or HLA-DR expression on CD3 lymphocytes compared with control subjects, but they had significantly lower numbers of total, CD3, CD4, and CD8 lymphocytes and a higher prevalence of anergy. Septic shock patients manifested an increase in neutrophil CD11b expression that may play a role in organ injury. In contrast, a more specific decrease in monocyte expression of functional antigens is also observed in patients with septic shock that may have implications for immunologic defense mechanisms.
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PMID:Altered leukocyte immunophenotypes in septic shock. Studies of HLA-DR, CD11b, CD14, and IL-2R expression. 768 46

Host inflammatory response to meningococcal infection is believed to be a major determinant of disease severity. Isogenic mutants of Neisseria meningitidis serogroup B1940, which differ in expression of capsular polysaccharide and lipooligosaccharide (LOS), were used to examine host responses in a whole blood model of bacteremia and a model of endothelial injury. The parent organism caused significantly less neutrophil shedding of the adhesion molecule, L-selectin, than the three mutant organisms (P < .01) and was most resistant to the bactericidal activity of whole blood. Despite marked differences in bacterial adhesion to endothelial cells (P < .05), no damage was induced by organisms alone. Endothelial injury was observed when neutrophils were incubated with adherent, capsule-deficient organisms (P < .05). The degree of endothelial damage was related to the number of neutrophils adherent to the endothelium. Thus, bacterial capsulation and LOS structure can influence neutrophil activation and endothelial injury and, as such, may be important in the pathogenesis of meningococcal sepsis.
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PMID:The influence of capsulation and lipooligosaccharide structure on neutrophil adhesion molecule expression and endothelial injury by Neisseria meningitidis. 853 55

The integrin CD11b is an important adhesion molecule mediating the transendothelial migration of circulating polymorphonuclear granulocytes into an inflammatory region. The expression of CD11b is closely related to the ability to polymerize actin, a major component of the cytoskeleton within the phagocyte. In this study we compared the CD11b expression as well as the polymerization of actin of isolated neutrophils from patients endangered by sepsis with cells from healthy donors. The patient population was subdivided into a group of patients with severe thermal injuries and a group of patients who were admitted to an intensive care unit on suspicion of sepsis. The following results were obtained: (1) cells from burn patients, but not from non-burn patients, showed a reduced basal expression of CD11b during the first week after the burn trauma; (2) stimulation with the chemotactic peptide formyl-Met-Leu-Phe (FMLP) led to a strong overexpression of CD11b on the cells from the burn patients, this effect was not observed using cells of the second subgroup; (3) the content of polymerized actin was reduced within resting and stimulated cells from burn patients during the first 2 weeks postinjury, non-burn patient cells showed an enhanced F-actin content within the first week; (4) the ability of burn and non-burn patient cells to polymerize actin after stimulation with FMLP was slightly impaired during the first week post injury/admission. The results demonstrate that cells from patients endangered by sepsis show dysfunctions on the level of adhesion molecule expression and the strongly related actin polymerization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of the adhesion molecule CD11b and polymerization of actin by polymorphonuclear granulocytes of patients endangered by sepsis. 855 83

Cellular adhesion is mediated by distinct cell surface receptors (adhesion molecules) and plays a pivotal role in the biological processes of morphogenesis, cell migration and cell-cell communication. During the past decade many adhesion molecules have been identified and structurally analysed. This has allowed an understanding of their role in the pathophysiology of disease, including inflammation and sepsis, ischaemia and reperfusion, transplant rejection, atherosclerosis and thrombosis, angiogenesis and wound healing, as well as carcinogenesis and tumour metastasis. Understanding of the molecular mechanisms of cellular communication is not only vital for advances in surgical pathophysiology, it also has the potential to widen the spectrum of diagnosis and therapy of disease. Analysis of expression of individual surface molecules may help in the diagnosis of transplant rejection and allow a prognostic determination of tumour progression and metastasis formation. Moreover, manipulation of adhesion molecule function by monoclonal antibodies, antisense oligonucleotides or single gene products may open the door for novel therapeutic regimens to prevent transplant rejection and ischaemia-, sepsis- and shock-induced tissue injury.
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PMID:Adhesion molecules as determinants of disease: from molecular biology to surgical research. 868 99

Multiple organ failure (MOF) is a common complication of sepsis or septic shock. In this condition, it is believed that activated neutrophils adhere to the vascular endothelium and induce various mediators and tissue damage, leading to organ damage. We investigated the plasma levels of inflammatory cytokine activating neutrophils, soluble adhesive molecules, and endotoxin in 8 patients with septic MOF, 15 patients with sepsis but without MOF, and in 5 patients with MOF unrelated infection. The soluble intercellular adhesion molecule-1 (sICAM-1) concentration in sepsis-complicated groups was significantly higher than that in the multiple organ failure (MOF) group without infection. Of sepsis-complicated groups, the sICAM-1 value in the MOF group was significantly higher than that in the sepsis group without MOF. In sepsis-complicated groups, both soluble endothelial-leukocyte adhesion molecule-1 (sELAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentrations were significantly higher than those in the MOF group without infection. However, there was no significant difference between the septic MOF group and the sepsis group without MOF. In patients showing high levels of soluble adhesion molecule, prognosis was poor, and the concentration of soluble adhesion molecules rapidly decreased during recovery from MOF. It is speculated that endotoxin and inflammatory cytokines damage vascular endothelium as well as various other cells and produce, a large number of adhesion molecule, especially in patients with septic MOF, causing leakage of adhesion molecules into blood.
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PMID:Levels of soluble adhesion molecules and cytokines in patients with septic multiple organ failure. 887 95


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