Transmigration |
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Leukocytes migrate across
resting endothelium if an exogenous chemoattractant
is present (Huang et al 1992; Furie
et al 1989; Furie
et al 1991). For example, addition of a gradient of IL-8 or fMLP results
in transmigration, which is dose dependent and can cause 50-90% of the
neutrophils to transmigrate (Furie
et al 1991; Smith
et al 1991; Smith
et al 1994). This has been termed "leukocyte driven" or chemotactic
transmigration. The pathophysiological hallmark of established inflammatory
transmigration is endothelial activation, an event requiring transcription
and protein synthesis. As a result adhesion molecules are upregulated,
inflammatory mediators are produced, and the endothelium secretes chemoattractants,
all of which contribute to transmigration. Endothelial are critical for
transmigration. They are secreted in significant amounts: concentrations
in vitro reach those producing maximal chemotactic responses (Smith,
1994). The stimulus for endothelial activation in vivo is probably
local production of cytokines and other inflammatory mediators released
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