Intracutaneous Injection of Lysophosphatidylcholine Induces Skin Inflammation and Accumulation of Leukocytes

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Abstract
Various cell stimuli act through activation of phospholipase A2, which hydrolyses fatty acids from membrane phospholipids, resulting in the formation of fatty acids and lysophospholipids. One of the lysophospholipid classes, lysophosphatidylcholine, is a chemoattractant for monocytes and T-lymphocytes and induces the expression of adhesion molecules on cultured endothelial cells. The purpose of the present study was to determine whether lysophosphatidylcholine possesses proinflammatory properties in vivo. This was assessed clinically and histologically by intracutaneous injection of 200-800 nmol lysophosphatidylcholine in healthy volunteers. Lysophosphatidylcholine elicited a dose- and time-dependent local erythema and oedema. The erythema disappeared within 4 h, while the induration lasted for up to 48 h. HE-stained biopsies taken after 24 h showed a leukocytoclastic vasculitis in 2 of the 6 subjects. Microscopic examination of immunohistochemically stained biopsies taken 24 h after the injection showed a significant increase in the number of T-lymphocytes, monocytes and neutrophils, whereas the number of Langerhans' cells was unchanged after lysophosphatidylcholine injection. In addition, the number of intercellular cell adhesion molecule-1 and -3-positive cells was increased approximately 3-fold after injection of lysophosphatidylcholine. In conclusion, the phospholipase A2 hydrolysis product lysophosphatidylcholine can induce erythema, oedema, a mixed cellular infiltrate and the expression of adhesion molecules.