Lysophosphatidylcholine and the inflammatory action of neutrophils.
Lysophosphatidylcholine (lysoPC) is a polar lipid formed in cells and tissues under normal conditions and is known to cause tissue damage in a variety of experimental systems. We have therefore examined the possibility that increased amounts of lysoPC are formed in activated inflammatory cells and are involved in their tissue-damaging action. Human neutrophil leucocytes were labelled with [14C]arachidonic acid (AA), activated with the calcium ionophore A23187, and the degradation of phospholipids, with subsequent release of AA and AA metabolites, was studied. We also studied neutrophil metabolism of [14C]lysoPC in the presence of different concentrations of cold lysoPC, and the relation between phospholipid degradation and release of N-acetyl-beta-glucosaminidase (NAG), a lysosomal enzyme. We found that the release of both AA and NAG was coupled to a degradation of phosphatidylcholine (PC), and that the neutrophils were able to metabolise lower, but not higher, concentrations of lysoPC. Moreover, the phospholipase A2 inhibitor, nordihydroguaiaretic acid significantly inhibited PC degradation, lysoPC formation, and NAG release, whereas the lipoxygenase inhibitor, BW 755C had little effect on these parameters. These findings demonstrate that the AA mobilization in activated neutrophils is associated with PC degradation, and point to be possibility that the ensuing lysoPC formation might mediate lysosomal enzyme release.
Lindahl
M
M
Department of Occupational Medicine, Linköping University, Sweden.
Bruhn
R
R
Tagesson
C
C
D000118:Acetylglucosaminidase / Q000378:metabolism; D000328:Adult; D001095:Arachidonic Acids / Q000493:pharmacokinetics*; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D007249:Inflammation / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2
D001095:Arachidonic Acids; D002135:Calcium-Binding Proteins; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; C025673:calciphorin; D010741:Phospholipases A; D054467:Phospholipases A2; D000118:Acetylglucosaminidase