Quo vadis macrophage activation - Role of phospholipids in the elicitation of the oxidative burst in macrophages

E. Pick, Y. Bromberg

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We propose that LK (and, possibly, non-LK) induced MP activation is mediated by a change in MP phospholipid metabolism, the result of which is the facilitation of phospholipase activation upon subsequent encounter with a membrane stimulant (bacteria, protozoa, tumor cells). The facilitated phospholipase activation will result in: a more intense OB with the consequent increase in the amount of toxic oxygen radicals produced; and an increase in the amount of unsaturated fatty acids released upon membrane stimulation; part of these fatty acids will generate toxic hydroperoxides by the action of cellular lipoxygenase or via the direct action of O2- and H2O2 produced in the course of the OB. The nature of the LK-induced phospholipid modulation is, at present, unknown. The most likely possibilities are: an increase in the overall quantity of certain phospholipids in the MP membrane, such as arachidonate-containing phosphatidylcholine, possibly synthesized by the methylation pathway; an increase in the amount of phospholipid in specific membrane domains surrounding critical receptors for potential OB stimulants; inhibition of acyl transferase activity, resulting in a more marked accumulation of free fatty acid upon phospholipase activation; or a modulatory effect on the two pathways of fatty-acid oxidation. Thus, a predominance of lipoxygenase over cyclooxygenase would cause a more intense OB because of the ability of hydroxy-fatty acids to stimulate O2- production as opposed to the lack of activity of prostaglandins. An 'indomethacin-like' effect of LK on MPs was proposed by Remold-O'Donnell and Remold in another context. An active lipoxygenase pathway could also generate potentially toxic hydroperoxy-fatty acids. Which of these alternative proposals is closest to the truth will only become apparent when subjected to systematic experimental scrutiny.

Original languageEnglish
Pages (from-to)570-574
Number of pages5
JournalTransplantation Proceedings
Issue number3
StatePublished - 1982


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