Oxidative stress promotes blood cell-endothelial cell interactions in the microcirculation.
Oxidative stress occurs when the production of reactive oxygen species (ROS) exceeds the capacity of the cell to detoxify these potentially injurious oxidants using endogenous antioxidant defense systems. Conditions associated with oxidative stress include ischemia/reperfusion, hypercholesterolemia, diabetes, and hypertension. The adhesion of circulating blood cells (leukocytes, platelets) to vascular endothelium is a key element of the pro-inflammatory and prothrombogenic phenotype assumed by the vasculature in these and other disease states that are associated with an oxidative stress. There is a growing body of evidence that links the blood cell endothelial cell interactions in these conditions to the enhanced production of ROS. Potential enzymatic sources of ROS within the microcirculation include xanthine oxidase, NAD(P)H oxidase, and nitric oxide synthase. ROS can promote a pro-inflammatory/prothrombogenic phenotype within the microvasculature by a variety of mechanisms, including the inactivation of nitric oxide, the activation of redox-sensitive transcription factors (e.g., nuclear factor-kappaB) that govern the expression of endothelial cell adhesion molecules (e.g., P-selectin), and the activation of enzymes (e.g., phospholipase A(2)) that produce leukocyte-stimulating inflammatory mediators (e.g., platelet-activating factor). The extensively documented ability of different oxidant-ablating interventions to attenuate blood cell endothelial cell interactions underscores the importance of ROS in mediating the dysfunctional microvascular responses to oxidative stress.
Cooper
Dianne
D
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Stokes
Karen Y
KY
Tailor
Antiben
A
Granger
D Neil
DN
D000818:Animals; D001773:Blood Cells / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D008833:Microcirculation / Q000166:cytology / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*