Tonic inhibition of chemotaxis in human plasma.
We found exaggerated chemotaxis in plasma treated with EDTA and thought that the EDTA might itself be inhibiting a tonic inhibitor(s) of chemotaxis. Our plasma fractionations suggested that evidence should be sought for a lipid moiety carrying this activity, and on spectrometry (LC-MS-MS together with GC-MS analyses), the biologically active but not the inactive fraction contained oleic and arachidonic acids. Because fatty acids are largely protein bound, we flooded plasma preparations with delipidated albumin, reasoning that it would bind enough fatty acids, including inhibitory ones, to counter their tonic inhibition. Indeed, we observed dramatic increases in chemotaxis. Hence, adding delipidated albumin to plasma has a similar effect to that of adding EDTA--amplification of the chemotactic response. Oleic acid in physiologic concentrations diminishes the magnifying effects of both EDTA and of delipidated albumin, and in fact diminishes the chemotactic response even without the presence of the amplifiers of chemotaxis. In contrast, arachidonic acid amplifies further the effect of EDTA but not of delipidated albumin, and this augmentation appears to be caused by an EDTA-dependent enrichment of the chemotactic gradient with leukotriene B4 (LTB4). We conclude that oleic acid, the blood levels of which vary among individuals, is at least one tonic inhibitor of chemotaxis in plasma.
Malawista
Stephen E
SE
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. stephen.malawista@yale.edu
de Boisfleury Chevance
Anne
A
van Damme
Jo
J
Serhan
Charles N
CN
D016718:Arachidonic Acid / Q000494:pharmacology; D001773:Blood Cells / Q000166:cytology* / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003470:Culture Media; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019301:Oleic Acid / Q000494:pharmacology; D012709:Serum Albumin / Q000494:pharmacology
D001798:Blood Proteins; D003470:Culture Media; D016209:Interleukin-8; D012709:Serum Albumin; D007975:Leukotriene B4; D016718:Arachidonic Acid; D019301:Oleic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D004492:Edetic Acid