Editors' ChoiceImmunology

Suppressing Chemotaxis

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Science Signaling  25 Nov 2008:
Vol. 1, Issue 47, pp. ec403
DOI: 10.1126/scisignal.147ec403

Malawista et al., a research group that previously found that polymorphonuclear leukocytes (PMNs) in plasma treated with the divalent cation chelating agent EDTA showed a prolonged chemotactic response, undertook a search for a tonic inhibitor of chemotaxis that might be susceptible to inhibition by this chelator. Analysis of fractions of leukocyte-conditioned medium subjected to controlled pore glass chromatography and heparin-Sepharose affinity chromatography suggested that the inhibitor was not a protein but a lipid. Liquid chromatography tandem mass spectrometry together with gas chromatography–mass spectrometry revealed that oleic acid and arachidonic acid were present in a biologically active—but not an inactive—fraction. Although physiological concentrations of oleic acid suppressed the exaggerated chemotactic response elicited by EDTA, arachidonic acid enhanced it. Noting that fatty acids bind albumin, the authors determined that, like EDTA, delipidated human serum albumin amplified the PMN chemotactic response; oleic acid suppressed the exaggerated response to albumin, whereas arachidonic acid did not affect it. In fact, the ability of arachidonic acid to enhance chemotaxis depended on EDTA, and pharmacological analysis suggested that this synergistic effect involved the EDTA-dependent generation of the chemoattractant leukotriene B4 (LTB4) from the added arachidonic acid. Oleic acid, however, inhibited chemotaxis in the absence of either EDTA or delipidated albumin; moreover, it inhibited the chemotactic response to LTB4, interleukin-8, and the peptide fMLP (N-formyl-methionyl-leucyl-phenylalanine). The authors thus conclude that oleic acid represents a tonic inhibitor of PMN chemotaxis that could perhaps be manipulated for anti-inflammatory purposes.

S. E. Malawista, A. de Boisfleury Chevance, J. van Damme, C. N. Serhan, Tonic inhibition of chemotaxis in human plasma. Proc. Natl. Acad. Sci. USA 105, 17949–17954 (2008). [Abstract] [Full Text]

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