Báo cáo y học: Nitric oxide, leukocytes and microvascular permeability: causality or bystanders

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Nitric oxide, leukocytes and microvascular permeability: causality or bystanders?
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Báo cáo y học: "Nitric oxide, leukocytes and microvascular permeability: causality or bystanders" Available online http://ccforum.com/content/12/1/104CommentaryNitric oxide, leukocytes and microvascular permeability:causality or bystanders?Balázs Hauser1,2, Martin Matejovic3 and Peter Radermacher11Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Parkstrasse 11, 89073 Ulm, Germany2Aneszteziológiai és Intenzív Terápiás Klinika, Semmelweis Egyetem, H-1125 Kietvolgyi, Budapest, Hungary31. Interni klinika, Karlova univerzita Praha, Lekarska fakulta a Fakultni nemocnice, Allej Svobody 80, 30460 Plzen, Czech RepublicCorresponding author: Peter Radermacher, peter.radermacher@uni-ulm.dePublished: 16 January 2008 Critical Care 2008, 12:104 (doi:10.1186/cc6214)This article is online at http://ccforum.com/content/12/1/104© 2008 BioMed Central LtdSee related research by Hollenberg et al., http://ccforum.com/content/11/6/R125Abstract synthase (iNOS) on leukocyte adhesion and rolling as well as on microvascular leakage. In this model, the authors hadIncreased microvascular permeability resulting in tissue edema is a previously shown that iNOS–/– mice presented with improvedhallmark of sepsis-related microcirculatory failure, and leukocyte– microvascular catecholamine responsiveness and, ultimately,endothelium interaction is thought to assume major importance inthis context. However, the role of nitric oxide (NO) in the interplay enhanced survival [2]. As expected, in the present study CLPof inflammation, leukocyte–endothelium interaction and increased itself aggravated leukocyte rolling and adhesion. Interestingly,microcirculatory permeability is still a matter of debate. Hollenberg deletion of iNOS did not affect this response, whereas itet al. now report, in the previous issue of Critical Care, that neither attenuated microvascular permeability. In sham-operatedgenetic deletion nor pharmacologic blockade of the inducible control mice, iNOS-derived NO inhibited the interactionisoform of the NO synthase (iNOS) affected the sepsis-related between leukocytes and endothelial cells (rolling andaggravation of leukocyte rolling and adhesion, whereas iNOSinhibition attenuated microvascular permeability. The authors adhesion), but not microvascular permeability. The authorsconclude that excess NO resulting from iNOS activation is concluded that excess NO resulting from iNOS activation isimportant in modulating vascular permeability during sepsis, but important in modulating vascular permeability during sepsis,that this effect is independent of its action on leukocytes. but that this effect is independent of its action on leukocytes.Increased microvascular permeability resulting in tissue How do these findings compare with the available literatureedema is a hallmark of sepsis-related microcirculatory failure, on the role of NO in leukocyte–endothelium interaction andand in this context leukocytes are thought to assume major microvascular permeability?importance. However, the role of nitric oxide (NO) in theinterplay of inflammation, leukocyte–endothelium interaction More than a decade ago, Kubes et al. showed that non-and increased microcirculatory permeability is still a matter of selective NO synthase inhibition increased leukocytedebate. It is well established that NO has a pivotal role in the adherence [3]. This effect was closely related to oxidativeregulation of vasomotor tone as well as in host defense and stress resulting from an enhanced production of superoxideimmune function, and abundant literature is available on both radicals [4], thus demonstrating the importance of NO as anits protective and its detrimental properties, which depend on oxygen radical scavenger. In rats with CLP, non-selective NOthe source of its release (for example, isoenzyme activation), synthase inhibition also increased leukocyte migration [5].the timing and the amount of its production, and the redox Activation of iNOS seemed to be responsible for the protec- tive properties of NO, because iNOS–/– mice challenged withstatus of the surrounding milieu. In the previous issue ofCritical Care, Hollenberg et al. [1] added another piece to lipopolysaccharide presented with a comparably increasedthis complex puzzle. Using a well-established, clinically accumulation of pulmonary leukocytes [6]. Furthermore, iNOS–/– caused enhanced pulmonary inflammation afterrelevant murine model of resuscitated, hyperdynamic sepsisresulting from cecal ligation and puncture (CLP) [2], the instillation of lipopolysaccharide into t ...