Lipoxin A4 inhibits phosphoinositide hydrolysis in human neutrophils

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Abstract

Lipoxins (LX) are trihydroxytetraene metabolites derived from arachidonic acid via an interaction between the 5- and 15-lipoxygenases. Preincubation of [3H] myo-inositol labeled PMN with 10−7M and 10−5M LXA4 for 1 minute at 37°C resulted in a concentration dependent inhibition of the generation of [3H] IP3 and [3H] IP in cells subsequently stimulated by increasing doses of LTB4 or FMLP for 1 minute at 37°C. Preincubation of PMN with LXA4 did not inhibit specific binding of [3H] LTB4 to PMN. These results indicate that LXA4 inhibits chemotactic factor-induced phosphoinositide hydrolysis at a post-receptor level.

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    Citation Excerpt :

    They were since found to be generated in humans in vivo during cell–cell interactions and in diverse tissues, with their diminished production observed in several human diseases [121]. Lipoxins possess numerous anti-inflammatory bioactivities towards neutrophils, including inhibition of chemotaxis, adhesion, migration, superoxide generation, MAC1 expression, and IP3 formation [124–133]. An extensive review of this area can be found in Ref. [121].

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