Comparison of endothelial activation during endotoxic and posttraumatic conditions by serum analysis of soluble e-selectin in nonhuman primates

Kneidinger, R.; Bahrami, Soheyl; Redl, Heinz; Schlag, G.; Robinson, Martyn K.

doi:10.1016/s0022-2143(96)90049-9

Cited by 26 publications

(9 citation statements)

References 11 publications

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“…In humans, biological responses are apparent at doses as small as 4 ng/kg [25] whereas in other species doses of 1 mcg/kg (rabbits [26], sheep [27]) or as high as 2 mg/kg (rats [28], pigs [29], and non-human primates [30,31,32,33]) are required for response. The difference in endotoxin activity between species is a confounding factor in preclinical studies in animals towards defining the role of endotoxin as a mediator in the pathogenesis of GN infections and in the development of anti-endotoxin antibodies.…”

Section: Structure Activitymentioning

confidence: 99%

Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect

Hurley

2013

Toxins

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Endotoxin is a potent mediator of a broad range of patho-physiological effects in humans. It is present in all Gram negative (GN) bacteria. It would be expected that anti-endotoxin therapies, whether antibody based or not, would have an important adjuvant therapeutic role along with antibiotics and other supportive therapies for GN infections. Indeed there is an extensive literature relating to both pre-clinical and clinical studies of anti-endotoxin antibodies. However, the extent of disconnect between the generally successful pre-clinical studies versus the failures of the numerous large clinical trials of antibody based and other anti-endotoxin therapies is under-appreciated and unexplained. Seeking a reconciliation of this disconnect is not an abstract academic question as clinical trials of interventions to reduce levels of endotoxemia levels are ongoing. The aim of this review is to examine new insights into the complex relationship between endotoxemia and sepsis in an attempt to bridge this disconnect. Several new factors to consider in this reappraisal include the frequency and types of GN bacteremia and the underlying mortality risk in the various study populations. For a range of reasons, endotoxemia can no longer be considered as a single entity. There are old clinical trials which warrant a re-appraisal in light of these recent advances in the understanding of the structure-function relationship of endotoxin. Fundamentally however, the disconnect not only remains, it has enlarged.

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Section: Structure Activitymentioning

confidence: 99%

Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect

Hurley

2013

Toxins

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“…Some authors suggested that endothelial P-selectin is unlikely to contribute to plasma sP-selectin concentration [23]. Anyway, assaying a specific platelet (e.g., β-thromboglobulin) and/or endothelial [e.g., soluble E-selectin (sE-selectin)] [25, 26]activation marker together may help to clarify the origin of elevated sP-selectin concentration. Interleukin-6 (IL-6) stimulates megakaryocytopoiesis and is likely to have a physiological role in this process [27, 28, 29, 30, 31, 32, 33, 34, 35].…”

Section: Introductionmentioning

confidence: 99%

Selectins and IL-6 during the Clinical Course of Idiopathic Thrombocytopenic Purpura

et al. 1999

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‘Stress thrombocytes’, i.e. large and presumably hyperfunctioning platelets, is a well-known characteristic of patients with idiopathic thrombocytopenic purpura (ITP). Therefore, despite what may be severe thrombocytopenia these patients generally do not suffer from severe life-threatening hemorrhage. The plasma level of soluble P-selectin (sP-selectin) is a valuable marker reflecting platelet activation. Available data suggest that interleukin-6 (IL-6) may contribute to the regulation of megakaryocytopoiesis and platelet activity. The purpose of this study is to investigate the status and kinetics of IL-6 and selectins, which are involved in the platelet function, production, and immunologic functions, during the clinical course of ITP, that may be helpful for understanding the biology of the disease. Twenty-two ITP patients were studied prospectively in the course of their disease. Sixteen, 8 and 6 patients were available after platelet recovery, relapse and splenectomy, respectively. Fifteen healthy persons served as a control group. Higher levels of both sP-selectin and IL-6 were observed in all clinical stages of disease compared to the control group. However, more prominent elevations were present during active stages of ITP, i.e. pretreatment (p < 0.001 vs. control group for both sP-selectin and IL-6) and relapse periods (p < 0.001 vs. control group for both sP-selectin and IL-6). Pretreatment soluble L-selectin and soluble E-selectin levels were not different from the controls. Both sP-selectin (r = –0.32, p = 0.019) and IL-6 (r = –0.41, p = 0.002) levels inversely correlated with platelet count during disease course. There was a positive correlation between the sL-selectin level and leukocyte count (r = 0.60, p < 0.001). These results suggest that residual platelets are activated in ITP, which offers a relatively benign clinical course compared to other thrombocytopenias. High IL-6 concentration during thrombocytopenia may be involved in compensatory megakaryocytopoiesis and augmented ‘residual platelet’ functions in ITP.

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“…Some sP-selectins are generated from endothelial cells [1]. On the other hand, increases in sE-selectin in the blood can be used to quantify endothelial activation [10]. The lack of elevation of sE-selectin in the present study indicates minimal activation of the epithelium.…”

mentioning

confidence: 65%

Fiberoptic bronchoscopy induces platelet activation

et al. 2006

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Comparison of endothelial activation during endotoxic and posttraumatic conditions by serum analysis of soluble e-selectin in nonhuman primates

Cited by 26 publications

References 11 publications

Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect

Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect

Selectins and IL-6 during the Clinical Course of Idiopathic Thrombocytopenic Purpura

Fiberoptic bronchoscopy induces platelet activation

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