Mechanisms and consequences of cell activation in the microcirculation.
Cells undergo activation in response to a wide range of stimuli. In vascular cells (leukocytes, endothelial cells, and platelets), the different forms of activation include degranulation, oxygen free radical formation, expression of membrane adhesion proteins, and biophysical changes such as pseudopod formation and increased cytoplasmic viscosity. Cell activation and low flow are common features of many cardiovascular diseases. There is evidence that plasma from patients contains an activating factor for neutrophils as well as other vascular cells. Activated neutrophils have the ability to impair microcirculatory transit by elevation of endothelial permeability, leukocyte adhesion to the endothelium, leukocyte capillary plugging, release of vasoactive products, and capillary deformation and compression due to oxygen-radical-mediated interstitial edema and cell dysfunction. In addition to reduced organ perfusion, cell activation can also cause cell dysfunction via release of cytotoxic mediators. A lower degree of neutrophil activation prior to acute circulatory challenge (i.e., low preactivation) correlates with improved survival rates after challenge and suggests that elevated levels of in vivo cell preactivation is a risk factor for cell injury and organ failure. Under conditions of low in-vivo cell preactivation (e.g., as is the case in endotoxin-tolerant animals), there is reduced tissue injury and lower mortality after challenge. We hypothesize that in-vivo cell preactivation due to everyday activity (infection, diet, smoking) may be a mechanism for microvascular low blood flow with leukocyte accumulation and may represent a risk factor for various cardiovascular diseases.
Department of Bioengineering, University of California, San Diego, La Jolla 92093-0412, USA.
M C
MC
Mazzoni
G W
GW
Schmid-Schönbein
D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D002318:Cardiovascular Diseases / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology; D006801:Humans; D008833:Microcirculation / Q000276:immunology*; D018375:Neutrophil Activation / Q000502:physiology*; D051381:Rats; D014655:Vascular Resistance / Q000502:physiology