Intrinsic 5-lipoxygenase activity is required for neutrophil responsivity.

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Guidot DM, Repine MJ, Westcott JY, Repine JE

Intrinsic 5-lipoxygenase activity is required for neutrophil responsivity.

Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8156-9.

PubMed ID

8058773 [ View in PubMed

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Abstract

We found that intrinsic neutrophil 5-lipoxygenase activity was necessary for human neutrophil adherence and chemotaxis in vitro and human neutrophil-mediated acute edematous injury in isolated perfused rat lungs given interleukin 8 intratracheally. Treatment with either Zileuton (a specific reversible competitive inhibitor of 5-lipoxygenase) or MK886 (a specific irreversible inhibitor of the 5-lipoxygenase activator protein) prevented stimulated neutrophil adherence and chemotaxis (but not superoxide anion production) in vitro. Zileuton- or MK886-inhibited neutrophil chemotaxis was not restored by adding leukotriene B4 in vitro. Perfusion with neutrophils and either Zileuton or MK886, or with MK886-pretreated neutrophils (without adding MK886 to the perfusate), also prevented lung injury (reflected by lung weight gain and lung Ficoll retention) and perfusate leukotriene B4 increases in isolated rat lungs given interleukin 8 intratracheally. Again, adding leukotriene B4 to the perfusate did not damage interleukin 8-treated isolated lungs perfused with Zileuton-inhibited neutrophils. We conclude that intrinsic 5-lipoxygenase activity is required for neutrophil adherence and chemotaxis and neutrophil-mediated lung injury.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Zileuton	Arachidonate 5-lipoxygenase	Protein	Humans	Yes	Inhibitor	Details