Effect of fatty acid structure on neutrophil adhesion, degranulation and damage to endothelial cells

• Published in: Atherosclerosis 1995-08, Vol.116 (2), p.247-259
• Main Authors: Bates, Edna J., Ferrante, Antonio, Smithers, Lisa, Poulos, Alf, Robinson, Brenton S.
• Format: Article
• Language: English
• Subjects: Adherence; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Adhesion - drug effects; Degranulation; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Fatty Acids, Omega-3 - chemistry; Fatty Acids, Omega-6; Fatty Acids, Unsaturated - chemistry; Granulocytes; Humans; Lipoxygenase - pharmacology; Medical sciences; Molecular Structure; n-3 and n-6 Polyunsaturated fatty acids; Neutrophils - cytology; Neutrophils - drug effects; Prostaglandin-Endoperoxide Synthases - pharmacology; Unsaturated fatty acids
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/0021-9150(95)05553-9

Neutrophils have been implicated in ischaemic heart disease, unstable angina pectoris and acute myocardial infarction. Alterations in dietary levels of specific 18- and 20-carbon polyunsaturated fatty acids have significant clinical benefits in cardiovascular disease. However, to date there has been no concerted effort to identify the structural basis for polyunsaturated fatty acid-induced alterations in key neutrophil functions. We have investigated the influence of fatty acid structure and involvement of lipoxygenase/cyclooxygenase pathways on fatty acid-induced neutrophil functions. When neutrophils were incubated with 18-carbon fatty acids containing one to four double bonds (10–33 μmol/l), a significant increase in adherence and release of specific granule constituents occurred compared with control cells. In general, as the number of double bonds in the 18-carbon fatty acid increased, so did its ability to stimulate these functions. There was less stimulation of adherence and specific granule release by 18:3(n-3) than its isomer 18:3(n-6). Smaller effects were seen on azurophilic granule release. A further increase in adherence and degranulation was observed with increasing carbon chain length (20:3(n-6) and 20:4(n-6)). Differences were found in the ability of isomers of 20:3 to stimulate neutrophil function. Of the fatty acids tested only 20:4(n-6) was able to induce significant neutrophil-mediated endothelial detachment. Introduction of either internal hydroperoxy or hydroxyl groups into 20:4(n-6) abolished its adherence stimulating activity and considerably reduced its ability to stimulate release of both specific and azurophilic granules. Preincubation of neutrophils with either lipoxygenase (caffeic acid) or cyclooxygenase (indomethacin) inhibitors had no effect on 20:4(n-6) stimulated function. These studies show that the number and position of double bonds, carbon chain length and oxidation state can be critical to the neutrophil stimulatory properties of these fatty acids.