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-3 Fatty acids suppress monocyte adhesion to human
endothelial cells: role of endothelial PAF generation
1 Medizinische Klinik II, Justus Liebig University, D-35392 Giessen; and 2 Medizinische Klinik mit Schwerpunkt Infektiologie, Charité, Humboldt University, D-13353 Berlin, Germany
Monocyte-endothelium interaction is a
fundamental process in many acute and chronic inflammatory diseases.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are fish
oil-derived alternative (
-3) precursor fatty acids implicated in the
suppression of inflammatory events. We investigated their influence on
rolling and adhesion of monocytes to human umbilical vein endothelial cells (HUVEC) under laminar flow conditions in vitro. Exposure of HUVEC
to tumor necrosis factor (TNF-
) strongly increased 1) surface expression of intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and E-selectin, 2)
platelet-activating factor (PAF) synthesis as assessed by thrombin
challenge, and 3) rate of rolling and adhesion of monocytes.
Preincubation of HUVEC with EPA or DHA markedly suppressed PAF
synthesis, monocyte rolling, and adherence, whereas expression of
endothelial adhesion molecules was unchanged. Also, PAF receptor
antagonists markedly suppressed the adhesion rate of monocytes, and EPA
or DHA revealed no additional inhibitory capacity. In contrast,
arachidonic acid partially reversed the effect of the antagonist. We
conclude that -3 fatty acids suppress rolling and adherence of
monocytes on activated endothelial cells in vitro by affecting
endothelial PAF generation.
eicosapentaenoic acid; arachidonic acid; adhesion molecules; leukocytes; platelet-activating factor
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