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

The importance of adhesion in regulating locomotion and accumulation of polymorphonuclear leukocytes (PMN) has remained vague. We found that the chemotaxis of human PMN resuspended in heat-inactivated plasma was maximal toward 1-10 nM N-formyl-met-leu-phe (f-Met-Leu-Phe), but fell below random motility toward >/= 100 nM. This impressive decrease of motility was paralleled by increased cell adherence on Petri dishes being minimal at 1 nM and maximal at >10 nM f-Met-Leu-Phe (6+/-1 and 37+/-2% [SE] adherent cells, respectively). Checked by phase-contrast microscopy, cells under stimulated adhesion lost the typical bipolar shape of moving PMN and became immobilized and highly flattened. PMN, preexposed to 250 nM f-Met-Leu-Phe and tested after washing, retained increased adhesiveness and showed extremely low random and chemotactic motility. In contrast, preexposure to 1 nM f-Met-Leu-Phe had no effect on chemotaxis. Supporting the concept that immobilizing hyperadhesiveness does not correspond to a general functional hyporesponsiveness of PMN, no depression of the initial ingestion rate was observed in the presence of 250 nM f-Met-Leu-Phe. Moreover, a close correlation was found between the induction of PMN adhesiveness and the stimulation of the hexose monophosphate pathway activity as well as of lysomal enzyme release (r >/= 0.98). Thus, "chemotactic deactivation" and "high-dose inhibition of chemotaxis" by N-formyl peptides is the consequence of increased cell adhesiveness. This phenomenon provides a mechanism for cell trapping at the inflammatory site. Conversely, if operative in circulating blood, e.g., in septicemia, it may impair PMN emigration to such sites.
 ...
PMID:Modulating influence of chemotactic factor-induced cell adhesiveness on granulocyte function. 44 62

Leukocyte activation is a property of systemic infection. Animal experiments indicate interleukin-1 (IL-1) as a possible modulator, while contradictory results have been reported from in-vitro stimulation of isolated leukocytes. The purpose of the present study was to investigate the activation of isolated polymorphonuclear (PMN) leukocytes in vitro by preparations of recombinant human IL-1 beta and IL-1 receptor antagonist, which in earlier studies could elicit and abrogate, respectively, a sepsis-like syndrome in rabbits. They have also been shown to influence acute phase protein synthesis in mice and rats, and release of leukocyte cathepsin G in vivo. It was found that recombinant human IL-1 beta elicited a dose-dependent luminol-enhanced chemiluminescence response in isolated human PMN leukocytes in the dose range 8.8 x 10(-11)-8.8 x 10(-8) M. The effect could be blocked by prior treatment with the IL-1 receptor antagonist, indicating a direct effect on the specific IL-1 receptor. Preincubation by IL-1 beta enhanced the effect of a secondary challenge with phorbol 12-myristate 13-acetate or formyl-Met-Leu-Phe by 30-40%. The priming effect of rhIL-1 beta could also be blocked by the specific receptor antagonist. In this study, incubation of PMN leukocytes with rhIL-1 beta failed to induce degranulation of both azurophil (neutrophil proteinase 4/proteinase 3) and specific (lactoferrin) granules. rhIL-1 beta has been shown to induce degranulation in vivo, which is thus indicated as an indirect effect. We conclude that IL-1 beta is a direct and specific, but probably weak stimulator of the PMN leukocyte.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Stimulation of human polymorphonuclear leukocytes by recombinant human interleukin-1 beta. 162 64

Production of superoxide anion by polymorphonuclear leukocytes (PMNL) was studied in donors and patients with burns. N-formyl-L-Met-L-Leu-L-Phe (FMLP) was used as an activator of PMNL. Evaluation in production of superoxide anion, caused by the activating effect of FMLP, proved to be useful as a diagnostic and prognostic criterion. 56 preparations of blood were studied in 21 patients with burns within the periods of acute burns toxemia, burns septicotoxemia and convalescence. Superoxide anion generating activity correlated with the disease severity: content of superoxide anion was distinctly decreased within the period of sepsis development. At the same time, complex treatment of the patients, involving step-by-step autodermoplastics, antibacterial preparations and immunotherapy, enabled to restore the superoxide anion production up to normal values. Evaluation of the superoxide anion generating activity by PMNL in the patients with severe forms of burns enabled to estimate the state of cell immunity in the patients depending on severity of burns trauma, period of burn disease and adequacy of the treatment applied.
 ...
PMID:[Enzymatic production of superoxide by human polymorphonuclear leukocytes in burns]. 285 Dec 10

Polymorphonuclear leukocyte (PMN) function was investigated in two patients with glycogen storage disease type IB and neutropenia. Glycogen storage disease type IB was documented by liver biopsy and a normal amount of latent glucose-6-phosphatase activity. Patient A had stomatitis, skin infections, and septicemia; patient B had respiratory infections, periodontitis, and oral candidiasis. Absolute neutrophil counts ranged from 114 to 2580/mm3. Diminished and delayed migration of PMN into a skin "window" occurred in B. Random and directed PMN migration under agarose toward f-Met-Leu-Phe, pepstatin A, and zymosan-activated serum were severely diminished in both patients. At 10(-7) M f-Met-Leu-Phe, mean random and directed migration were 52 and 23% (A, n = 3) and 48 and 13% (B, n = 4) of controls. These results were independent of incubation time and chemoattractant concentration. Patients' PMN had diminished quantitative nitroblue tetrazolium reduction compared to controls. B had a significant defect in PMN bactericidal activity with Escherichia coli with less than 0.2 log killing at 2 h. These results further characterize the defect in PMN migration reported by Beaudet et al. (J Pediatr 97:906, 1980). The finding of other abnormalities of PMN function suggests a metabolic defect in the neutrophil which may be related to the microsomal membrane defect in hepatocytes in glycogen storage disease type IB.
 ...
PMID:Impaired chemotaxis and neutrophil (polymorphonuclear leukocyte) function in glycogenosis type IB. 345 31

The appearance of the adult respiratory distress syndrome (ARDS) during the course of acute illness is believed to result, in part, from intrapulmonary neutrophil sequestration and degranulation induced by circulating inflammatory mediators. To evaluate the role of complement-neutrophil interactions in the pathogenesis of ARDS in man, 34 patients suffering from intra-abdominal sepsis (seven), multisystem trauma (15), or acute pancreatitis (12) were serially studied with regard to neutrophil migratory responses to C5a and F-Met-Leu-Phe, lysosomal content of beta-glucuronidase and lysozyme, and simultaneously obtained plasma levels of immunoreactive C3adesArg and C5adesArg. Nineteen patients developed ARDS. In these patients, plasma C3adesArg levels obtained within 72 hours of admission to the hospital were elevated to 305 +/- 35 ng/ml compared with 145 +/- 16 ng/ml for patients who did not develop ARDS (p less than 0.0005). C5adesArg levels were not elevated in either group. In vitro studies showed that neutrophils from normal persons were able to clear all of the C5a/C5adesArg generated in up to 5% zymosan-activated serum, while no clearance of C3adesArg was identified. Patient migratory responses could be divided into three groups based on their initial (less than 72 hour) samples: (1) hyperresponsive to both N = formyl-methionyl-leucyl-phenylalanine (FMLP) and C5a, (2) specifically deactivated to C5a, and (3) deactivated to both C5a and FMLP. Patients in the latter two groups developed ARDS. Enzyme content of neutrophils from patients who developed ARDS showed a substantial fall in beta-glucuronidase and lysozyme levels. The finding of elevated plasma C3a levels and deactivation of migratory response to C5a support the contention that complement activation had occurred in these patients and that their neutrophils had been exposed to C5a/C5adesArg in vivo. The finding of nonspecific migratory dysfunction associated with lysozymal enzyme loss, a circumstance not reproducible in vitro by C5a exposure, suggests that other stimuli produced degranulation of neutrophils made hyperresponsive by prior exposure to C5a.
 ...
PMID:Complement activation and clearance in acute illness and injury: evidence for C5a as a cell-directed mediator of the adult respiratory distress syndrome in man. 400 15

Long-term results of 13 liver transplantations in patients with a previous diagnosis of type I familial amyloid polyneuropathy (FAP) are presented. The diagnosis of type I FAP was based on the presence of a biochemical marker in the plasma (TTR-Met-30 in 11 patients, TTR-Ala-71 in two). Maximum follow-up is 28 months and the survival rate stands at 11 of 13 patients. Two patients died from sepsis at 2 and 6 months. TTR disappeared from plasma in all cases. Neurological status improved in all eight patients undergoing transplantation more than 6 months previously, although electromyographic studies showed a slight improvement only in the six with follow-up of more than 1 year. All 13 patients showed a hyperdynamic haemodynamic pattern with a high incidence (four patients) of the use of venovenous bypass due to haemodynamic intolerance. Two patients also received transplants by the 'piggy-back' technique. In conclusion, liver transplantation may be useful in the treatment of certain patients with FAP to halt and improve the neurological consequences of the disease.
 ...
PMID:Clinical improvement after liver transplantation for type I familial amyloid polyneuropathy. 762 23

Ecotin, a serine protease inhibitor found in the periplasm of Escherichia coli, has been characterized as a potent reversible tight-binding inhibitor of the human contact activation proteases factor XIIa (FXIIa) and plasma kallikrein, having Ki values of 89 pM and 163 pM, respectively. Ecotin also inhibited human leukocyte elastase (HLE) with high affinity (Ki = 55 pM). The association rate constants kon for FXIIa and kallikrein were 5.3 x 10(5) M-1.s-1 and 2.9 x 10(5) M-1.s-1, respectively. The dissociation rate constant koff for kallikrein, measured in the presence of HLE to prevent reassociation, was 6.3 x 10(-5) s-1; the koff for ecotin with FXIIa was 4.7 x 10(-5) s-1. Both FXIIa and kallikrein cleaved ecotin slowly at pH 5.0, identifying Met-84 as the P1 residue. The potent anticoagulant effect by ecotin is explained by the coincident inhibition of FXIIa, kallikrein, and FXa and suggests that it may be useful in the study of inflammatory or thrombotic disorders such as sepsis or cardiopulmonary bypass.
 ...
PMID:Ecotin is a potent inhibitor of the contact system proteases factor XIIa and plasma kallikrein. 778 71

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)
 ...
PMID:Expression of the adhesion molecule CD11b and polymerization of actin by polymorphonuclear granulocytes of patients endangered by sepsis. 855 83

The role of T-lymphocytes (T cells) and interferon-gamma (IFN-gamma) in the pathogenesis of sepsis-induced microvascular endothelial injury remains unclear. We sought to determine whether the syngeneic coculture of human T cells in the presence of LPS promoted subsequent neutrophil (PMN)-mediated endothelial cytotoxicity. Syngeneic T cells were cocultured with 51Cr-loaded human adipose microvascular endothelial cell (HAMVEC) monolayers in the absence and presence of LPS. Subsequent PMN-mediated HAMVEC cytotoxicity (measured as percent specific 51Cr release) was absent in cultures that contained T cells but no LPS and was significantly increased when T cells were cocultured in the presence of LPS. This was true both following addition of unstimulated PMNs (-0.8 +/- 3.0% vs 4.9 +/- 4.7% for T cells alone vs T cells plus LPS, respectively) and PMNs stimulated with f-Met-Leu-Phe (-0.4 +/- 3.1% vs 10.7 +/- 3.0% for T cells alone vs T cells plus LPS, respectively). Increased cytotoxicity was associated with increased expression of the endothelial adhesion molecules ICAM-1 and VCAM-1. Control experiments failed to demonstrate cytotoxicity when HAMVEC were cultured in the presence of IFN-gamma alone, LPS alone, or T cells without LPS. It appears that there is a necessary requirement of both LPS and (presumably activated) T cells or their products (other than IFN-gamma) for enhanced PMN-mediated endothelial cytotoxicity. This phenomenon may also be mediated by increased expression of endothelial adhesion molecules that promote subsequent PMN adhesion.
 ...
PMID:Endotoxin-induced, neutrophil-mediated endothelial cytotoxicity is enhanced by T-lymphocytes. 920 40

Patients with sepsis and acute lung injury have increased interleukin (IL)-18 levels systemically. We hypothesize that IL-18 stimulates neutrophils (PMNs) at physiologic concentrations. IL-18 primed the oxidase at 15 min (10-100 ng/ml), 30 min (0.1-100 ng/ml), and 60 min (100 ng/ml; P<0.05) and caused translocation of p47(phox) to the membrane similar to lipopolysaccharides. CD11b surface expression was increased by IL-18 in a time- and concentration-dependent manner. IL-18 caused up-regulation of the formyl-Met-Leu-Phe receptor, changes in PMN size, and elastase release. Investigation of signaling demonstrated IL-18-mediated activation of p38 mitogen-activated protein (MAP) kinase in a concentration (0.1-100 ng/ml)-, time (5-15 min)-, and Ca2+-dependent manner. IL-18 directly increased cytosolic Ca2+ concentration. IL-18 activation of PMNs was blocked by inhibition of p38 MAP kinase activity (SB203580) or by inhibition of p38 MAP kinase activation by chelation of cytosolic Ca2+. We conclude that IL-18, at physiologic concentrations, is an effective PMN priming agent that requires p38 MAP kinase activity.
 ...
PMID:Physiological levels of interleukin-18 stimulate multiple neutrophil functions through p38 MAP kinase activation. 1214 32


1 2 3 Next >>