Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To further investigate the neutrophil dysfunction of newborn infants, we have measured expression of the neutrophil Fc gamma receptors FcRIII and FcRII in extremely immature preterm neonates born at 24 to 32 weeks of gestation. Fc receptor expression was measured by FACS analysis of cells stained with monoclonal antibody Leu11b for FcRIII and IV-3 for FcRII. "Well" preterm neonates displayed reduced FcRIII, 51.05 +/- 2.0 (mean fluorescence channel +/- SE) when compared with term neonates, 69.24 +/- 5.5 and adult controls, 71.83 +/- 3.0. "Stressed" preterm neonates with severe respiratory distress syndrome or septicemia had a further downregulation of FcRIII, 32.67 +/- 3.0 and 35.75 +/- 1.8, respectively, associated with grossly abnormal cellular fluorescence distribution. In well preterm neonates, expression of FcRIII improved to adult levels during the first two postnatal weeks, suggesting a postnatal maturation of function. Stressed neonates had signs of partial neutrophil activation (increased Mac-1 expression and chemotactic ability), leading us to propose that the further downregulation of FcRIII may be due to receptor shedding in vivo by partially activated cells. FcRII expression was found to be equivalent to adult levels in both well preterm and stressed neonates. Reduced neutrophil FcRIII expression may provide some explanation for the reported abnormalities of phagocytosis and bacterial killing in preterm neonates.
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PMID:Abnormal FcRIII expression by neutrophils from very preterm neonates. 216 29

In vitro studies have shown that phagocytic cells are capable of undergoing activation in response to inflammatory signals and that the activation process is quite complex. A relationship between polymorphonuclear leukocyte (PMN) Fc receptor-mediated phagocytosis and oxidative metabolism has been seen in humans. We have sequentially examined circulating polymorphonuclear leukocytes (PMNs) from a total of 13 postoperative swine with either no sepsis, untreated intraabdominal sepsis, or treated intraabdominal sepsis to determine phagocytic activity over 8 postoperative days (POD). Products of the oxidative burst (i.e., myeloperoxidase) reduced the phagocytic activity of nonseptic swine PMN. Phagocytic activity was augmented by inhibiting the nonseptic swine oxidative burst with 10 mM sodium azide (an inhibitor of myeloperoxidase). In swine with untreated intraabdominal sepsis, PMN Fc receptor-mediated phagocytosis exhibited a biphasic response. An initial (between POD1 and POD4) increase in PMN function was followed by a subsequent (between POD4 and POD8) decrease in PMN function. Partial preservation of phagocytic capability was seen when swine were reexplored on POD4 and had their intraabdominal sepsis treated. These results indicate that (1) as in humans, nonseptic swine PMN Fc receptor-mediated phagocytosis is augmented by inhibition of the PMN respiratory burst; (2) untreated intraabdominal sepsis produces an initial increase and subsequent decrease in PMN Fc receptor-mediated phagocytosis; (3) early treatment of intraabdominal sepsis results in partial restoration of PMN Fc receptor-mediated phagocytosis.
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PMID:Intraabdominal sepsis: effects on polymorphonuclear leukocyte Fc receptor-mediated phagocytosis. 235 94

Thrombocytopenia is a frequent and sometimes insidious complication of anticoagulant therapy with heparin. Two types of heparin-induced thrombocytopenia with a distinct aetiology have been recognized. Type I is characterized by a mild thrombocytopenia of early onset which requires careful monitoring but usually not the cessation of heparin therapy. The mild thrombocytopenia is probably due to the mild pro-aggregatory properties of heparin and can be more severe in the presence of other predisposing factors, e.g. sepsis. Type II heparin-induced thrombocytopenia is more severe and usually occurs after a period of 7-10 days. Heparin therapy should be ceased immediately and other anticoagulant therapy initiated. The thrombocytopenia is believed to be due to the development of a heparin-dependent antibody that causes platelet aggregation and release. The precise mechanism of heparin-dependent antibody-platelet interaction is still not entirely clear but probably involves the binding of an antibody-heparin immune complex to the platelet Fc receptor.
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PMID:Heparin-induced thrombocytopenia. 264 53

Reduced concentrations of glutamine (GLN) in plasma and skeletal muscle, defective host defense systems, and a diminished expression of the HLA-DR antigen on monocytes are important diagnostic parameters for late post-injury sepsis. In this in vitro study, we investigated whether blood monocyte-derived macrophage antigen expression and function from healthy donors is influenced by GLN. Lowering the GLN concentration in culture medium from 2 mmol/L to 200 mumol/L reduced the expression of HLA-DR by 40% (P < .001) on monocyte-derived macrophages, and decreased tetanus toxoid-induced antigen presentation. In addition, low GLN levels downregulated the expression of intercellular adhesion molecule-1 (ICAM-1/CD54), Fc receptor for IgG (Fc gamma RI/CD64), and complement receptors type 3 (CR3; CD11b/CD18) and type 4 (CR4; CD11c/CD18). A correlation was found between the phagocytosis of IgG-sensitized ox erythrocytes or opsonized Escherichia coli and the decreased expression of Fc gamma RI and CR3. Monocyte expression of CD14, CD71, and Fc gamma RIII/CD16 and capacity to phagocytose latex beads were not affected by altering the level of GLN. Depletion of GLN was associated with a significant reduction in cellular adenosine triphosphate (ATP), which may have influenced cell surface marker expression and phagocytosis. It remains to be seen whether these in vitro findings are of clinical significance in the treatment of sepsis.
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PMID:Influence of glutamine on the phenotype and function of human monocytes. 763 65

Immune complexes containing human gamma (g)1 or murine g2a antibodies generate secondary effector mechanisms via Fc receptor binding or complement activation, whereas those containing human g4 or murine g1 antibodies generally do not. Therefore, isotype selection of therapeutic antibodies may have important clinical consequences. In a rabbit model of human tumor necrosis factor (rhuTNF)-induced pyrexia, a murine/human chimeric g4 anti-human TNF-alpha monoclonal antibody (mAb) (cCB0011) showed a dose-dependent inhibition of pyrexia, whereas a g1 isotype variant of the same mAb gave a marked pyrexia that was seen at all doses indicative of an immune complex-mediated response. To investigate whether isotype difference could influence mAb efficacy in pathological disease states, hamster/murine chimeric g1 and g2a anti-murine TNF-alpha mAbs (TN3g1, TN3g2a) were studied in experimental shock in mice and rats. In lipopolysaccharide-induced shock in mice, treatment with TN3g1 mAb at 30 and 3 mg/kg resulted in 90% survival by 72 h (p < or = 0.004), and prolonged survival to 45 h (p < or = 0.05), respectively, compared with 100% mortality by 27 h in controls. In contrast, a g2a isotype variant of the same mAb (30 mg/kg) resulted in only 10% survival by 72 h (p < or = 0.05). In a neutropenic sepsis model in rats there was greater survival in animals receiving the g1 isotype of TN3 compared with g2a isotype variant (70 vs. 27%; p < or = 0.005) with 100% mortality in the controls. These differences were not due to the pharmacokinetic profiles of the mAbs. In models of experimental shock antibody isotype can affect outcome with inactive isotypes (human g4 and murine g1) being more efficacious than active isotypes (human g1 and murine g2a).
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PMID:Differential effect of isotype on efficacy of anti-tumor necrosis factor alpha chimeric antibodies in experimental septic shock. 811 78

In this study we have investigated the ability of lipopolysaccharide (LPS) to suppress binding and phagocytosis of erythrocytes via various receptors on mouse macrophages. Thioglycollate-elicited peritoneal macrophages were treated in vitro with LPS and the ability to bind and phagocytose radiolabeled sheep red blood cells was determined. We show that LPS can directly suppress phagocytosis of immunoglobulin G-opsonized and nonopsonized sheep red blood cells (SRBCs) by inflammatory macrophages. Suppression was dose dependent and was observed after 4 h of exposure. This effect lasted for at least 24 h following the removal of LPS. LPS suppressed the binding, rate, and absolute level of phagocytosis via Fc receptors. Phagocytosis via all Fc receptors (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) was suppressed by LPS. Furthermore, suppression was not limited to Fc receptor-mediated phagocytosis because binding and uptake of C3bi-opsonized SRBCs to CR3 receptors was also decreased following LPS treatment. LPS did not exert its effects via the production of interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha, or interferon alpha/beta, because antibodies to these cytokines did not abrogate the effect. The ability of LPS to suppress binding and phagocytosis of microorganisms may contribute to the toxic effects of LPS during gram-negative sepsis by preventing or delaying elimination of bacteria by host macrophages.
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PMID:Lipopolysaccharide-induced suppression of erythrocyte binding and phagocytosis via Fc gamma RI, Fc gamma RII, Fc gamma RIII, and CR3 receptors in murine macrophages. 833 82

Despite systematic antibiotic therapy, severe infections (septicemia, meningitis, or osteomyelitis) are a major cause of mortality and morbidity in children with sickle cell disease (SCD). In this study, we explored the possibility that polymorphism at the human leukocyte antigen (HLA) locus might constitute an immunogenetic modifying factor to the intrinsic susceptibility to infection in patients with SCD. A cohort of 80 SCD patients living in Paris, 43 with at least one major infectious complication and 37 without infections, were typed for HLA class II loci by polymerase chain reaction-sequence-specific primers (PCR-SSP). We found that significantly more patients without infections carry the HLA class II DRB1*15 specificity than did patients with infections (21.6% in the first group, versus 4.7% in the second group; chi(2) = 10.47, p(c) = 0.01), supporting a protective effect of this allele. Conversely, significantly more patients were found to carry the DQB1*03 specificity within the group of severe infections, supporting a negative effect (34.9% versus 12.2%, chi(2) = 9.41, p(c) = 0.01). These findings suggest a direct involvement of HLA polymorphism in the development of major infections in SCD. Together with previous data on polymorphism of the Fc receptor and of the mannose-binding lectin, they provide evidence for a polygenic immunomodulation of the constitutively increased infectious risk in SCD.
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PMID:Infectious complications in sickle cell disease are influenced by HLA class II alleles. 1187 37

The phenotype and function of peripheral blood monocytes change after trauma and during sepsis. The aim of the study was to evaluate monocyte expression of human leucocyte antigen (HLA)-DR and Fc receptor III (FcR III) (CD16) in neonates and small children with high risk of sepsis (hospitalized at the intensive care unit). The reduced proportion of CD14+HLA-DR+ monocytes was observed in all patients at the intensive care unit, while the increase of CD16 expression on monocytes was observed in the course of sepsis. The measurement of CD16 expression on monocytes also proved to be more useful for monitoring patient. The proportion of both CD14dimCD16+ and CD14highCD16+ monocytes increased during sepsis; however, monocytes showed reduced ability to phagocytose Escherichia coli, compromised ability to cooperate with T cells and reduced CD86 expression in parallel to HLA-DR depression. The reduced interleukin (IL)-1 but rather increased IL-10 production was associated with sepsis. The differences between CD14+CD16+ monocytes of healthy donors and patients with sepsis are discussed.
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PMID:CD14+CD16+ monocytes in the course of sepsis in neonates and small children: monitoring and functional studies. 1202 67

The immune response to infection must be controlled to ensure it is optimal for defense while avoiding the consequences of excessive inflammation, which include fatal septic shock. Mice deficient in FcgammaRIIb, an inhibitory immunoglobulin G Fc receptor, have enhanced immune responses. Therefore, we examined whether FcgammaRIIb controls the response to Streptococcus pneumoniae. Macrophages from FcgammaRIIb-deficient mice showed increased antibody-dependent phagocytosis of pneumococci in vitro, and consistent with this infected FcgammaRIIb-deficient mice demonstrated increased bacterial clearance and survival. In contrast, previously immunized FcgammaRIIb-deficient mice challenged with large inocula showed reduced survival. This correlated with increased production of the sepsis-associated cytokines tumor necrosis factor alpha and interleukin 6. We propose that FcgammaRIIb controls the balance between efficient pathogen clearance and the cytokine-mediated consequences of sepsis, with potential therapeutic implications.
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PMID:FcgammaRIIb balances efficient pathogen clearance and the cytokine-mediated consequences of sepsis. 1498 Nov 11

Peripheral blood CD16 (Fc receptor for immunoglobulin G III)-positive monocytes have been shown to expand in different pathological conditions, such as cancer, asthma, sepsis, human immunodeficiency virus infection, and AIDS progression, but data in leishmaniasis are lacking. We found that cutaneous leishmaniasis patients (n = 15) displayed a significant increase in the percentage (3.5 vs. 10.1) as well as mean fluorescent intensity (13.5 vs. 29.2) of ex vivo CD16 expression in monocytes as compared with healthy controls. We observed a significant positive correlation between the percentage of ex vivo CD16+ monocytes and lesion size (P = 0.0052, r = 0.75) or active transforming growth factor-beta plasma levels (P = 0.0017, r = 0.78). In addition, two patients with nonhealing lesions during a 3-year follow-up had high (9.1-19.4%) CD16 levels at diagnosis. Our data suggest a deleterious role for CD16 in human leishmaniasis, as well as its possible use as a marker for disease severity and/or adverse disease outcome.
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PMID:CD16+ monocytes in human cutaneous leishmaniasis: increased ex vivo levels and correlation with clinical data. 1628 34


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