Essential fatty acid deficiency impairs macrophage spreading and adherence. Role of arachidonate in cell adhesion.
Dietary polyunsaturated fatty acid manipulation exerts a strikingly protective effect in models of tissue inflammation and injury. A critical element of this effect appears to revolve around leukocyte trafficking but underlying mechanisms are ill understood. In the current study it was observed that essential fatty acid (EFA) deficiency markedly impaired the capacity of resident macrophages to spread and adhere. This effect was not a simple function of the alteration of membrane fatty acid composition. Elicited EFA-deficient macrophages were equally adherent to elicited control cells, despite the fact that they were equally EFA-deficient relative to resident EFA-deficient cells. With respect to the mechanism underlying defective macrophage adherence in EFA deficiency, no change in the expression of cell surface adherence molecules (Fc receptor, Mac-1, or LFA-1) was noted with the deficiency state. Also, an adherence defect could not be induced in normal cells pharmacologically with cyclooxygenase blockade, lipoxygenase blockade, or a platelet-activating factor receptor antagonist. In contrast, phospholipase inhibition was able to induce a spreading and adherence defect in resident macrophages similar to that seen with EFA deficiency. Using several phospholipase inhibitors, a correlation between phospholipase inhibition and impairment of adherence was observed. Adding back exogenous fatty acids to cells after phospholipase inhibition demonstrated that normal adherence was reconstituted with arachidonate. This alteration in macrophage spreading and adherence with EFA deficiency may be an important component of the anti-inflammatory effect of dietary polyunsaturated fatty acid manipulation. Additionally, these results suggest that arachidonate may be an intracellular mediator of leukocyte adherence.
Lefkowith
J B
JB
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Rogers
M
M
Lennartz
M R
MR
Brown
E J
EJ
D000818:Animals; D001095:Arachidonic Acids / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D046508:Culture Techniques; D004591:Electrophoresis, Polyacrylamide Gel; D005228:Fatty Acids, Essential / Q000172:deficiency*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010740:Phospholipases / Q000494:pharmacology
D001095:Arachidonic Acids; D005228:Fatty Acids, Essential; D010740:Phospholipases