Human neutrophil elastase abolishes interleukin-8 chemotactic activity.

Abstract:

:A large body of literature supports the role of interleukin-8 (IL-8) in inflammatory lung disease. Numerous factors induce the local synthesis and secretion of this potent chemokine leading to the recruitment and activation of polymorphonuclear leukocytes. However, little is currently known about the fate of IL-8 secreted at sites of inflammatory injury. We have found that incubation of recombinant human IL-8 with purified human neutrophil elastase (HNE) results in the loss of IL-8 chemotactic activity in a dose- and time-dependent fashion. This loss in bioactivity is accompanied by a similar loss of IL-8 immunoreactivity. Western blot analysis revealed that IL-8 chemotactic activity is lost by proteolysis of the parent molecule into undetectable small fragments. The terminal digestion of IL-8 was specific to HNE as no loss of bioactivity was observed with equimolar concentrations of the serine proteases urokinase, plasmin, thrombin, or cathepsin G. This effect on chemotactic activity is not limited to recombinant IL-8 because HNE also digested IL-8 secreted by human monocytes. HNE-mediated proteolysis offers a novel mechanism for down-regulating the inflammatory cascade initiated by IL-8.

journal_name

J Leukoc Biol

authors

Leavell KJ,Peterson MW,Gross TJ

doi

10.1002/jlb.61.3.361

subject

Has Abstract

pub_date

1997-03-01 00:00:00

pages

361-6

issue

3

eissn

0741-5400

issn

1938-3673

journal_volume

61

pub_type

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