Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Detection of Lipocortin 1 in Human Lung Lavage Fluid: Lipocortin Degradation As a Possible Proteolytic Mechanism in the Control of Inflammatory Mediators and Inflammation

Susan F. Smith, Teresa D. Tetley, Abraham Guz and Roderick J. Flower
Environmental Health Perspectives
Vol. 85 (Apr., 1990), pp. 135-144
DOI: 10.2307/3430676
Stable URL: http://www.jstor.org/stable/3430676
Page Count: 10
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Detection of Lipocortin 1 in Human Lung Lavage Fluid: Lipocortin Degradation As a Possible Proteolytic Mechanism in the Control of Inflammatory Mediators and Inflammation
Preview not available

Abstract

Lipocortins are structurally related, glucocorticoid-inducible proteins that inhibit phopholipase A2 ( PLA2), thereby reducing the liberation of arachidonic acid from phospholipids and so limiting the synthesis of eicosanoid inflammatory mediators. This study is the first demonstration of one lipocortin, lipocortin 1 (Lc 1; 37 kDa), in human lung lavage supernatants. In lavage fluid from healthy volunteers, a higher percentage (> 70%) of the detected Lc 1 was in its native form, compared to that from patients with abnormal lungs. In patients' lavage fluids, Lc 1 was more likely to be partially degraded (34 kDa). In abnormal bronchoalveolar lavage fluid (BALF), the more polymorphonuclear neutrophils (PMN)/lavage, the lower the proportion of Lc 1 in the native (37 kDa) form (n = 7 pairs, rs = -0.8214, p < 0.05). Furthermore, when BALF cells were cultured and the harvested conditioned media incubated with pure human recombinant Lc 1, degradation of the 37 kDa form increased with the percentage of PMN (n = 10 pairs, s = -0.7200 after 1 hr; n = 6 pairs, rs = -0.9241 after 6 hr). These results suggest that factors released from the PMN are responsible for Lc 1 degradation in man. When recombinant human Lc 1 was incubated with human neutrophil elastase, the enzyme degraded Lc 1 in a dose-dependent way, suggesting that neutrophil elastase may be one such factor. Since PMNs are ubiquitous at sites of inflammation, it is possible that Lc 1 degradation is a permissive mechanism, which ensures that sufficient inflammation occurs to destroy the provocative stimulus. However, it is equally possible that, in some circumstances, the mechanism may be pathological and that the inactivation of Lc 1 leads to chronic, uncontrolled inflammation.

Page Thumbnails

  • Thumbnail: Page 
[135]
    [135]
  • Thumbnail: Page 
136
    136
  • Thumbnail: Page 
137
    137
  • Thumbnail: Page 
138
    138
  • Thumbnail: Page 
139
    139
  • Thumbnail: Page 
140
    140
  • Thumbnail: Page 
141
    141
  • Thumbnail: Page 
142
    142
  • Thumbnail: Page 
143
    143
  • Thumbnail: Page 
144
    144