Mc. Mazzoni et Gw. Schmidschonbein, MECHANISMS AND CONSEQUENCES OF CELL ACTIVATION IN THE MICROCIRCULATION, Cardiovascular Research, 32(4), 1996, pp. 709-719
Cells undergo activation in response to a wide range of stimuli. In va
scular cells (leukocytes, endothelial cells, and platelets), the diffe
rent forms of activation include degranulation, oxygen free radical fo
rmation, expression of membrane adhesion proteins, and biophysical cha
nges such as pseudopod formation and increased cytoplasmic viscosity.
Cell activation and low flow are common features of many cardiovascula
r diseases. There is evidence that plasma from patients contains an ac
tivating factor for neutrophils as well as other vascular cells. Activ
ated neutrophils have the ability to impair microcirculatory transit b
y elevation of endothelial permeability, leukocyte adhesion to the end
othelium, leukocyte capillary plugging, release of vasoactive products
, and capillary deformation and compression due to oxygen-radical-medi
ated interstitial edema and cell dysfunction. In addition to reduced o
rgan perfusion, cell activation can also cause cell dysfunction via re
lease of cytotoxic mediators. A lower degree of neutrophil activation
prior to acute circulatory challenge (i.e., low preactivation) correla
tes with improved survival rates after challenge and suggests that ele
vated levels of in vivo cell preactivation is a risk factor for cell i
njury and organ failure. Under conditions of low in-vivo cell preactiv
ation (e.g., as is the case in endotoxin-tolerant animals), there is r
educed tissue injury and lower mortality after challenge. We hypothesi
ze that in-vivo cell preactivation due to everyday activity (infection
, diet, smoking) may be a mechanism for microvascular low blood flow w
ith leukocyte accumulation and may represent a risk factor for various
cardiovascular diseases.