Lipid chemotaxins isolated from culture filtrates of Escherichia coli and from oxidized lipids.

Lipid extracts of sterile culture filtrates of Escherichia coli were shown to contain approximately 75% of the chemotactic activity for human polymorphonuclear leukocytes and rabbit alveolar macrophages. Fractionation and purification of these lipids revealed the presence of many unknown lipids of widely different properties, but all were anionic and at very low concentrations, chemotactic. The only one of active molecules that could be identified was an unsaturated ultraviolet-absorbing hydroxy fatty acid, which, following catalytic reduction with hydrogen, was found to be hydroxyeicosanoic acid. This fatty acid's chromatographic behavior was very similar to that of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), which is a potent chemotaxin for polymorphonuclear leukocytes and macrophages. Unknown chemotaxins could be generated by the oxidation of known unsaturated lipids. Prostaglandins A2 and E2 produced potent chemotaxins upon aerobic oxidation. Malonaldehyde, a peroxidation product of unsaturated lipids, when reacted with phosphatidylethanolamine in aerobic conditions, also produced strong chemotactic agents. The chemotactic activity of these products could be destroyed by catalytic reduction with hydrogen and by methylation with dry methanolic HCl. These data indicate that the nonenzymatic oxidation of unsaturated lipids generates some products that are potent chemotaxins for mammalian inflammatory cells.