The inflammatory response to endotoxin

Goodman, Max L.; Way, Barrie; Irwin, John W.

doi:10.1002/path.1711280103

Cited by 30 publications

(10 citation statements)

References 10 publications

(4 reference statements)

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“…Microvascular obstruction and endothelial injury related to leukoaggregation and endothelial adherence are pivotal in sepsis (10,11) and in reperfusion injury (12). Essential functions of PMN, one of the most important leukocyte subpopulations, include rolling on PMN, adherence and migration, and lysis of phagocyted pathogens by oxidative burst response.…”

Section: Discussionmentioning

confidence: 99%

Functional and phenotypic changes in polymorphonuclear neutrophils induced by catecholamines

Trabold

Gruber

Fröhlich

2007

Scandinavian Cardiovascular Journal

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Section: Discussionmentioning

confidence: 99%

Functional and phenotypic changes in polymorphonuclear neutrophils induced by catecholamines

Trabold

Gruber

Fröhlich

2007

Scandinavian Cardiovascular Journal

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“…Endotoxin (lipopolysaccharide, LPS) is a cell wall component of gram-negative bacteria, which reproduces many manifestations of gram-negative sepsis3,4 and is used frequently in experimental sepsis models. Endotoxemia promotes platelet adhesion to microvessels in vivo5-7, microvascular thrombosis8-10, and enhances light/dye-induced microvascular thrombosis6,11. While the mechanisms responsible for prothrombotic manifestations of endotoxemia remain to be fully understood, suggested mediators include P-selectin and von Willebrand factor (VWF).…”

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confidence: 99%

Differential Role of von Willebrand Factor and P-Selectin on Microvascular Thrombosis in Endotoxemia

Patel

Soubra

Dong

et al. 2008

ATVB

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Objective— Endotoxin (lipopolysaccharide [LPS]) enhances microvascular thrombosis in mouse cremaster venules. Because von Willebrand factor (vWF) and P-selectin are suggested to mediate LPS-induced platelet–microvessel interactions, we determined whether vWF and P-selectin contribute to microvascular thrombosis in endotoxemia. Methods and Results— A light/dye-induced thrombosis model was used in cremaster microvessels of saline or LPS-injected mice (wild-type, P-selectin–deficient, vWF-deficient, or littermate controls). In each strain except vWF-deficient mice, LPS enhanced thrombosis in venules, resulting in ≈30% to 55% reduction in times to thrombotic occlusion. LPS had no effect on thrombosis in vWF-deficient mice, although these mice had similar systemic responses to LPS (tachycardia, thrombocytopenia, and plasma coagulation markers). vWF-deficient mice demonstrated prolonged times to thrombotic occlusion relative to littermates. LPS increased plasma vWF in each strain studied. While immunofluorescence in wild-type mice failed to detect LPS-induced differences in microvascular vWF expression, it revealed markedly higher vWF expression in venules relative to arterioles. Conclusions— vWF mediates light/dye-induced microvascular thrombosis and endotoxin-induced enhancement of thrombosis in mouse cremaster venules; P-selectin is not required for enhanced thrombosis in response to endotoxin. Enhanced vWF expression in venules relative to arterioles has potential implications for the differences in thrombotic responses among these microvessels.

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“…Previous studies have established that endotoxin has a propensity for causing inflammation and vascular damage. A widespread inflammatory response consisting of swelling of endothelial cells, migration of neutrophils, edema, and extravasation of cellular elements has been reported in organs other than the brain (13). Light and ultrastructural techniques have documented the ability of endotoxin to damage the vascular endothelium (3,6, 11).…”

Section: Resultsmentioning

confidence: 99%

Systemic and Neuropathologic Effects of E. coli Endotoxin in Neonatal Dogs

1983

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Summarytional 2 0 4 samples of arterial blood were obtained hourly forThe acute systemic and neuropathologic effects of E. coli endotoxin were determined in neonatal dogs. Administration of sublethal (LDo), moderate (LD50), or lethal (LDlo0) doses of endotoxin produced significant arterial hypotension, metabolic (lactic) acidosis, and hypoglycemia. Neuropathologic changes consisted of widespread inflammation in both grey and white matter; however, necrotic lesions were found only in forebrain white matter.determination ofplasma glucose and lactate levels by fluorometric analysis according to the method of Lowry and Passoneau (19). Body temperature was monitored by means of a rectal thermocouple (Yellow Springs) and maintained by a servo-controlled heating lamp. After insertion of the catheter, halothane was withdrawn and the animals allowed to spbntaneously breathe room air. The wound was sutured and periodically infiltrated with xylocaine, 1%. A low (LDo), moderate (LD~o), or high (LDIoo) Bacterial infections in the human infant are an important cause of subsequent mental retardation, cerebral palsy, and epilepsy (18,22,23,25). The morbidity and mortality associated with perinatal bacterial infections have been attributed to bacterial endotoxin, a lipopolysaccharide component of the bacterial cell wall. Because administration of endotoxin to laboratory animals mimics human septicemia (1,4,8,14), the systemic and neuropathologic disturbances induced by endotoxin are of considerable interest.Studies by Gilles et al. (12) have shown that administration of E. coli endotoxin to newborn kittens produces extensive brain injury. The acute systemic changes occurring during neonatal endotoxemia have not been described in detail. We, therefore, undertook a series of experiments in neonatal dogs to determine the acute neuropathologic changes occurring during endotoxemia as well as the critical physiologic and and metabolic parameters (blood pressure, heart rate, arterial blood gases, glucose, and lactate levels), which might be associated with those neuropathologic changes. Although these systemic parameters have not been studied during endotoxemia in the neonatal dog, they have been shown to be important predictors of mortality in the endotoxintreated adult dog (5,9,17,20). MATERIALS AND METHODSDose-response curve. Mongrel dogs, 1-10 days of age, were selected because their state of neurologic development at birth resembles that of the human infant of approximately 34-40 wk gestation (16). Trials were conducted in 16 animals to determine the dose of E. coli endotoxin that would result in 0, 50, and 100% mortality when injected subcutaneously. A lyophilized preparation of endotoxin from E. coli 055:B5 (Difco Laboratories) was chosen because this organism is a pathogen for human neonates, may be transmitted by nursery personnel (28), and has been previously used in neuropathologic experiments (12).Systemic responses to graded endotoxemia. The physiologic and metabolic responses of the animals were examined before and after ...

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The inflammatory response to endotoxin

Cited by 30 publications

References 10 publications

Functional and phenotypic changes in polymorphonuclear neutrophils induced by catecholamines

Functional and phenotypic changes in polymorphonuclear neutrophils induced by catecholamines

Differential Role of von Willebrand Factor and P-Selectin on Microvascular Thrombosis in Endotoxemia

Systemic and Neuropathologic Effects of E. coli Endotoxin in Neonatal Dogs

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