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)

The purpose of this study was to examine how intra-abdominal sepsis and extracellular matrix proteins (fibronectin, laminin) affect adherent polymorphonuclear leukocyte (PMN) function. Two groups of swine were studied: Group I (n = 5) underwent sham laparotomy; Group II (n = 8) underwent cecal ligation and incision. PMN adherent to either fibronectin (F) or laminin (L) had increased candicidal activity over buffer (B) by Group I but not by post-operative day 8 Group II PMN. (Percent specific release 51Cr-Group I--35.00, 68.25, 64.75% for B, F, and L; P less than 0.001 comparing B vs. F or L; Group II--14.25, 12.50, 12.75% for B, F, and L; P = NS comparing B vs. F or L.) To determine the mechanism for this finding, PMN priming was then assessed by evaluating both PMN adherence to extracellular matrix proteins and the cell surface expression of CR1/CR3 by using sheep RBC opsonized with C3b or C3bi. PMN activation was assayed by using MTT-Formazan, myeloperoxidase, and hypochlorous acid (HOCl) production. Fibronectin and laminin increased PMN adherence and CR1/CR3 expression over buffer by Group I and Group II animals. Fibronectin and laminin increased MTT-Formazan, myeloperoxidase, and HOCl production over buffer by Group I PMN but not POD 8 Group II PMN. These results suggest that untreated intra-abdominal sepsis partially abrogates the effect of extracellular matrix proteins on PMN function; in particular, the activation but not priming of adherent PMN by extracellular matrix proteins is reduced in this clinical situation.
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PMID:Polymicrobial sepsis disrupts normal neutrophil extracellular matrix protein interactions. 132 74

Overwhelming sepsis continues to be a major source of morbidity and mortality in patients who have sustained severe traumatic injury. Recently, much interest has been focused on the role of the peripheral blood neutrophil (PMN) in infections in these patients. Two surface receptors, CD11b (CR3) and CD16 (Fc gamma RIII), are thought to participate in bacterial phagocytosis and are both present on greater than 85% of normal PMNs. We have previously shown that cells that lack both of these receptors have markedly reduced phagocytic function. The purpose of this study was to determine the effect of severe trauma on the expression of these PMN receptors. Twenty severe trauma patients, age 19-70 years, presenting with an initial APACHE II score of greater than or equal to 10 were arbitrarily divided into two groups to define severity of injury: Group A, initial APACHE II of 10-18 (n = 11) and Group B, initial APACHE II of 19-25 (n = 9). Blood was obtained on admission, on Day 3, and weekly thereafter. PMNs were stained with fluorochrome-labeled monoclonal antibodies directed against CD11b and CD16 and then analyzed by flow cytometry. Controls consisted of 14 normal adults, age 20-65 years. The percentage and absolute numbers of CD11b+/CD16+ PMNs were determined for each patient or control sample. ANOVA and multiple comparison of variables (P = 0.05) were performed for each week. Values for Group A were different from controls at Weeks 0, 1, and 3. Values for Group B were significantly lower than those of controls at all weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced expression of neutrophil CD11b and CD16 after severe traumatic injury. 153 18

We investigated the effects of untreated intraabdominal sepsis on the interrelationship between PMN oxidative metabolism and cell surface receptor expression. Female swine underwent either sham laparotomy (n = 7) or cecal ligation and incision (n = 9) with assays conducted on postoperative days (POD) 0, 1, 4, and 8. Superoxide anion production, intracellular H2O2 production, and the cell surface expression of Fc gamma RII, III, CR1, and CR3 were measured. In addition, phagocytosis of serum-opsonized zymosan was used as a multivalent ligand for CR3 and subsequently Fc gamma RII, III, and CR1 expression were assayed to determine if intraabdominal sepsis induces a linkage between complement and Fc gamma receptor expression. Superoxide anion production increased between POD 0 and 4 and fell between POD 4 and 8 in animals with untreated intraabdominal sepsis. Intracellular H2O2 production rose between POD 0 and 1 and then fell progressively in animals with untreated intraabdominal sepsis. Simulation of the oxidative burst using glucose/glucose oxidase reduced Fc gamma RII and III expression in both sets of animals with a greater reduction seen by POD 4 in animals with intraabdominal sepsis. CR1/CR3 expression was increased with glucose/glucose oxidase by POD 4 in the presence of intraabdominal sepsis. Xanthine/xanthine oxidase did not alter cell surface receptor expression. Phagocytosis of serum-opsonized zymosan decreased subsequent Fc gamma RII expression in animals with intraabdominal sepsis by POD 4.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraabdominal sepsis: enhanced autooxidative effect on polymorphonuclear leukocyte cell surface receptor expression. 166 27

Because of the potential importance of interleukin 1 (IL-1) in modulating inflammation and the observations that human blood neutrophils (PMN) express IL-1 receptors (IL-1R) and synthesize IL-1 alpha and IL-1 beta, we studied the IL-1R on blood PMN from a group of patients with the sepsis syndrome. We report a marked enhancement in the sites per cell of IL-1R expressed on sepsis-PMN of 25 consecutively studied patients compared to 20 controls (patient mean = 9,329 +/- 2,212 SE; control mean = 716 +/- 42 SE, respectively). There was no demonstrable difference in the Kd of IL-1R on sepsis-PMN (approximately 1 nM) as determined by saturation curves of 125I-IL-1 alpha binding and the IL-1R on sepsis-PMN had an apparent Mr approximately 68,000, a value like that of normal PMN. Cytofluorographic analysis indicated that the sepsis-PMN phenotype is a single homogeneous population with respect to IL-1R expression. In contrast, expression of the membrane complement receptor CR3 is not increased on sepsis-PMN. Similar increases in expression of IL-1R were not observed in various other inflammatory processes, including acute disseminated inflammation and organ failure not caused by infection, acute infection without organ failure, and immunopathologies such as active systemic lupus erythematosus and rheumatoid arthritis. Enhanced expression of IL-1R was not related simply to the state of myeloid stimulation. Increased expression of IL-1R on normal PMN was induced in vitro by incubating cells with recombinant human granulocyte-macrophage/colony-stimulating factor for 18 h and this response was inhibited by cycloheximide, suggesting the possibility that de novo synthesis of IL-1R might occur in PMN during the sepsis syndrome.
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PMID:Increased expression of the interleukin 1 receptor on blood neutrophils of humans with the sepsis syndrome. 183 97

High dose melphalan (HDM 110-140 mg/m2) and total body irradiation (TBI, 10.5 Gy, single fraction) followed by infusion of autologous bone marrow (ABMT) was evaluated for toxicity and efficacy in 24 children with acute lymphoblastic leukaemia (ALL) in second (CR2) or third remission (CR3). Marrow was purged with Campath 1 in six children (four were children in CR3). All children had engraftment with a median of 30 days (range 18-70 days) to neutrophil count greater than 0.5 x 10(9)/l. Four children (16%) died from toxicity 1-4 months after autograft, two from pneumonitis, one from an intracerebral haemorrhage and one from sepsis. Apart from fever and mucositis the procedure was well tolerated. Nine of 17 children treated in CR2 remain in complete remission 6-72 months after ABMT (median 25 months). Seven of these have a follow-up of greater than 12 months. Three of the seven children treated in CR3 are alive 17, 22 and 29 months post ABMT. Seven children relapsed within 10 months (median 4 months) of the autograft. Only one relapse has occurred beyond 10 months. HDM and TBI followed by ABMT is a relatively well tolerated regimen and may contribute to survival in children with relapsed ALL.
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PMID:High dose melphalan and total body irradiation with autologous marrow rescue in childhood acute lymphoblastic leukaemia after relapse. 204 72

Polymorphonuclear leukocytes (PMN) and monocytes from 20 patients with acute bacterial infections were examined for phagocytic function. PMN of patients expressed markedly enhanced phagocytosis as measured by the ingestion of erythrocyte (E)IgG and IgG/C3b-coated E. Phagocytosis of E coated with C3b alone was not seen, while low levels of ingestion of iC3b-E by patients' PMNs was noted. Monocytes from patients and controls expressed similar phagocytic activity in a fixed endpoint assay; however, the kinetics of phagocytosis by patients' monocytes was strikingly faster. Superoxide anion (O2.) and myeloperoxidase activities were similar to controls in PMN of four patients studied on day 1 of admission. PMN from two of three patients studied longitudinally showed an initial elevation in EIgG phagocytosis, which fell to normal levels by day 4, concomitantly with increased O2. generation and clinical improvement. Phagocytosis remained elevated in the third patient who did not clear his septicemia. Surface membrane FcRII, FcRIII, CR1, and CR3 were similar on patient and control PMN. In contrast, FcRI was increased on PMN of five of seven patients by monomeric IgG binding, and on two of two patients by monoclonal anti-FcRI binding. Thus, PMN and monocytes of patients with acute bacterial infections are either upregulated with regard to phagocytic function or are less susceptible to downregulation than are normal cells. This presumably would have a beneficial effect on host defenses during infection.
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PMID:Studies on phagocytosis in patients with acute bacterial infections. 253 44

Two siblings with delayed separation of the umbilical cord, recurrent skin ulceration and dental sepsis were shown to have defective neutrophil phagocytosis of opsonized yeast (S. cerevisiae) and respiratory burst to opsonized and unopsonized zymosan. Increased activity in the NBT reduction test, normal ingestion and killing of S. aureus, and normal spontaneous and directional motility were also demonstrated. These abnormalities of neutrophil phagocytosis were confined to the affected siblings; their healthy parents and brother showed normal neutrophil function. Both children had a polymorph neutrophil leucocytosis, and had normal humoral and cell-mediated immunity. SDS electrophoresis of neutrophil cell membrane preparations showed absence of a glycoprotein band of 175,000 daltons, which was present in the parents' neutrophils in reduced amounts. OKMI monoclonal antibody, which recognized the C3bi receptor (CR3) failed to bind to the affected siblings neutrophils. The findings in these children emphasize the importance of this receptor in phagocytosis, and possibly other neutrophil functions.
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PMID:Familial defect of polymorph neutrophil phagocytosis associated with absence of a surface glycoprotein antigen (OKMI). 659 65

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

We report that, in rats, the lethal consequences of high-dose endotoxin challenge are exacerbated by the intravascular administration of prostaglandin E1 but attenuated by the intravascular administration of endocytosable particles. This protection is mediated by opsonins. Nonopsonizable particles were unable to provide protection unless first pseudoopsonized with antibody directed against the CR3 (CD11b/CD18) phagocyte receptor. We show that endogenously opsonized particles can act in concert with prostaglandin E1 (putatively by elevation of neutrophil intracellular cAMP and the resultant downregulation of CR3) to completely rescue animals from the lethal late-stage sequelae of experimental endotoxemia. These data illustrate that the interaction of particles with cellular receptors can transform the overall systemic response to prostaglandin E1 from pro- to antiinflammatory. This suggests a role for multiple receptor engagement events in defining the systemic prostaglandin response and offers a rationale for developing new therapeutic modalities in the treatment of sepsis and other inflammatory diseases.
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PMID:Endogenously opsonized particles divert prostanoid action from lethal to protective in models of experimental endotoxemia. 770 30

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


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