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Inflammatory response in microvascular endothelium in sepsis: role of oxidants.

Cepinskas G, Wilson JX - J Clin Biochem Nutr (2008)

Bottom Line: It is characterized by the excessive production of reactive oxygen species (ROS) both in the circulation and in the affected organs.The excessive generation of ROS inevitably leads to oxidative stress in the microvasculature and has been implicated as a causative event in a number of pathologies including sepsis.Changes in microvascular endothelial cells, the cell type that occurs in all organs, are discussed.

View Article: PubMed Central - PubMed

Affiliation: Centre for Critical Illness Research, Lawson Health Research Institute, 800 Commissioners Rd. E., London, Ontario, N6A 4G4, Canada.

ABSTRACT
Sepsis, as a severe systemic inflammatory response to bacterial infection, represents a major clinical problem. It is characterized by the excessive production of reactive oxygen species (ROS) both in the circulation and in the affected organs. The excessive generation of ROS inevitably leads to oxidative stress in the microvasculature and has been implicated as a causative event in a number of pathologies including sepsis. In this review, we focus on the role of oxidative and nitrosative stress during the early onset of sepsis. Changes in microvascular endothelial cells, the cell type that occurs in all organs, are discussed. The mechanisms underlying septic induction of oxidative and nitrosative stresses, the functional consequences of these stresses, and potential adjunct therapies for microvascular dysfunction in sepsis are identified.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of cellular responses in sepsis. Sepsis-related inflammatory mediators (e.g. LPS, TNF-α, etc.) present in blood plasma directly activate microvascular endothelial cells and leukocytes with respect to the increased production of oxidants, activation of inflammation-relevant transcription factor, NFκB, and up-regulation of pro-adhesive phenotype, resulting in an increased neutrophilic leukocyte (PMN) migration/accumulation in the tissues and microvascular dysfunction (solid dark arrows). That, in turn, leads to activation of residential macrophages and organ-specific parenchymal cells, which results in feedback activation of the microvascular endothelial cells and leukocytes (dark arrows). Subsequently, these cells further impair microvascular function, allowing pro-inflammatory mediators directly access from the blood to the interstitium (solid white arrow). Because of the systemic nature of the septic response, inflammation in each individual organ may be stimulated repeatedly by pro-inflammatory mediators that are released into the circulation by remote organs. If unchecked, sepsis leads to the multiple organ dysfunction and failure.
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Figure 1: Schematic diagram of cellular responses in sepsis. Sepsis-related inflammatory mediators (e.g. LPS, TNF-α, etc.) present in blood plasma directly activate microvascular endothelial cells and leukocytes with respect to the increased production of oxidants, activation of inflammation-relevant transcription factor, NFκB, and up-regulation of pro-adhesive phenotype, resulting in an increased neutrophilic leukocyte (PMN) migration/accumulation in the tissues and microvascular dysfunction (solid dark arrows). That, in turn, leads to activation of residential macrophages and organ-specific parenchymal cells, which results in feedback activation of the microvascular endothelial cells and leukocytes (dark arrows). Subsequently, these cells further impair microvascular function, allowing pro-inflammatory mediators directly access from the blood to the interstitium (solid white arrow). Because of the systemic nature of the septic response, inflammation in each individual organ may be stimulated repeatedly by pro-inflammatory mediators that are released into the circulation by remote organs. If unchecked, sepsis leads to the multiple organ dysfunction and failure.

Mentions: One of the key features of sepsis is tissue infiltration by phagocytic cells [9–13]. In this scenario, PMN and monocytes/macrophages respond to septic stimulation by producing reactive oxygen species (ROS) (e.g., superoxide, hydrogen peroxide) and reactive nitrogen species (RNS) (e.g., nitric oxide) [14]. In addition, PMN release granular enzymes (e.g. elastase, cathepsin) and the myeloperoxidase (MPO)-derived oxidant, hypochlorous acid (HOCl). All these components may contribute to PMN/macrophage-mediated killing of the bacteria. However, if produced in excess during SIRS and sepsis, the ROS, RNS and proteolytic enzymes cause microvascular dysfunction followed by organ dysfunction (Fig. 1).


Inflammatory response in microvascular endothelium in sepsis: role of oxidants.

Cepinskas G, Wilson JX - J Clin Biochem Nutr (2008)

Schematic diagram of cellular responses in sepsis. Sepsis-related inflammatory mediators (e.g. LPS, TNF-α, etc.) present in blood plasma directly activate microvascular endothelial cells and leukocytes with respect to the increased production of oxidants, activation of inflammation-relevant transcription factor, NFκB, and up-regulation of pro-adhesive phenotype, resulting in an increased neutrophilic leukocyte (PMN) migration/accumulation in the tissues and microvascular dysfunction (solid dark arrows). That, in turn, leads to activation of residential macrophages and organ-specific parenchymal cells, which results in feedback activation of the microvascular endothelial cells and leukocytes (dark arrows). Subsequently, these cells further impair microvascular function, allowing pro-inflammatory mediators directly access from the blood to the interstitium (solid white arrow). Because of the systemic nature of the septic response, inflammation in each individual organ may be stimulated repeatedly by pro-inflammatory mediators that are released into the circulation by remote organs. If unchecked, sepsis leads to the multiple organ dysfunction and failure.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2386519&req=5

Figure 1: Schematic diagram of cellular responses in sepsis. Sepsis-related inflammatory mediators (e.g. LPS, TNF-α, etc.) present in blood plasma directly activate microvascular endothelial cells and leukocytes with respect to the increased production of oxidants, activation of inflammation-relevant transcription factor, NFκB, and up-regulation of pro-adhesive phenotype, resulting in an increased neutrophilic leukocyte (PMN) migration/accumulation in the tissues and microvascular dysfunction (solid dark arrows). That, in turn, leads to activation of residential macrophages and organ-specific parenchymal cells, which results in feedback activation of the microvascular endothelial cells and leukocytes (dark arrows). Subsequently, these cells further impair microvascular function, allowing pro-inflammatory mediators directly access from the blood to the interstitium (solid white arrow). Because of the systemic nature of the septic response, inflammation in each individual organ may be stimulated repeatedly by pro-inflammatory mediators that are released into the circulation by remote organs. If unchecked, sepsis leads to the multiple organ dysfunction and failure.
Mentions: One of the key features of sepsis is tissue infiltration by phagocytic cells [9–13]. In this scenario, PMN and monocytes/macrophages respond to septic stimulation by producing reactive oxygen species (ROS) (e.g., superoxide, hydrogen peroxide) and reactive nitrogen species (RNS) (e.g., nitric oxide) [14]. In addition, PMN release granular enzymes (e.g. elastase, cathepsin) and the myeloperoxidase (MPO)-derived oxidant, hypochlorous acid (HOCl). All these components may contribute to PMN/macrophage-mediated killing of the bacteria. However, if produced in excess during SIRS and sepsis, the ROS, RNS and proteolytic enzymes cause microvascular dysfunction followed by organ dysfunction (Fig. 1).

Bottom Line: It is characterized by the excessive production of reactive oxygen species (ROS) both in the circulation and in the affected organs.The excessive generation of ROS inevitably leads to oxidative stress in the microvasculature and has been implicated as a causative event in a number of pathologies including sepsis.Changes in microvascular endothelial cells, the cell type that occurs in all organs, are discussed.

View Article: PubMed Central - PubMed

Affiliation: Centre for Critical Illness Research, Lawson Health Research Institute, 800 Commissioners Rd. E., London, Ontario, N6A 4G4, Canada.

ABSTRACT
Sepsis, as a severe systemic inflammatory response to bacterial infection, represents a major clinical problem. It is characterized by the excessive production of reactive oxygen species (ROS) both in the circulation and in the affected organs. The excessive generation of ROS inevitably leads to oxidative stress in the microvasculature and has been implicated as a causative event in a number of pathologies including sepsis. In this review, we focus on the role of oxidative and nitrosative stress during the early onset of sepsis. Changes in microvascular endothelial cells, the cell type that occurs in all organs, are discussed. The mechanisms underlying septic induction of oxidative and nitrosative stresses, the functional consequences of these stresses, and potential adjunct therapies for microvascular dysfunction in sepsis are identified.

No MeSH data available.


Related in: MedlinePlus