| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Surgery, University of Texas Southwestern Medical School and Veterans Affairs North Texas Health Care System, Dallas, Texas, USA
2 Department of Surgery, University of Texas Southwestern Medical School and Veterans Affairs North Texas Health Care System, Dallas, Texas, USA; Department of Orthopaedic Surgery, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark
3 Department of Physiology, University of Texas Southwestern Medical School and Veterans Affairs North Texas Health Care System, Dallas, Texas, USA
4 Department of Internal Medicine, University of Texas Southwestern Medical School and Veterans Affairs North Texas Health Care System, Dallas, Texas, USA
* To whom correspondence should be addressed. E-mail: rturna{at}lsuhsc.edu.
Reduced plasma concentrations of the extracellular actin-binding proteins gelsolin and Gc-globulin correlate with pulmonary failure and death in humans following injury. The purpose of this study was to investigate the role of plasma gelsolin in the pathophysiology of inflammation-induced lung injury. We postulated that plasma gelsolin levels decrease at an early time-point after burn injury and that the intravenous infusion of gelsolin prevents burn-induced pulmonary microvascular dysfunction. Adult Sprague-Dawley rats were randomized to undergo a 40% body surface area thermal injury (BURN) or manipulation without burn (SHAM). Plasma gelsolin and Gc-globulin concentrations were determined at various times during the first 6 days of injury by western blotting. Other animals were randomized to receive either recombinant human gelsolin (0.078, 0.78 or 7.8 mg) or albumin (7.8 mg) before and eight hours following BURN or SHAM. Twenty four hours later, pulmonary microvascular permeability was assessed by measuring the capillary filtration (Kf) using an isolated, perfused lung model. We found that plasma gelsolin levels of burn-injured rats decreased to 10% of normal levels within 12 hrs and remained below normal levels for up to 6 days post-injury. Gc-globulin values also fall, but to a lesser extent, and only transiently. Treatment of burned animals with intravenous infusions of recombinant human gelsolin prevented the increase in pulmonary microvascular permeability that accompanies this injury. Our findings are consistent with the hypothesis that plasma gelsolin depletion contributes to the pathophysiology of pulmonary microvascular dysfunction during inflammation.
This article has been cited by other articles:
|
|
 |
|
  L. J. Page, J. Y. Suk, L. Bazhenova, S. M. Fleming, M. Wood, Y. Jiang, L. T. Guo, A. P. Mizisin, R. Kisilevsky, G. D. Shelton, et al. Secretion of amyloidogenic gelsolin progressively compromises protein homeostasis leading to the intracellular aggregation of proteins PNAS, July 7, 2009; 106(27): 11125 - 11130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-S. Lee, K. Sampath, S. A. Karumanchi, H. Tamez, I. Bhan, T. Isakova, O. M. Gutierrez, M. Wolf, Y. Chang, T. P. Stossel, et al. Plasma Gelsolin and Circulating Actin Correlate with Hemodialysis Mortality J. Am. Soc. Nephrol., May 1, 2009; 20(5): 1140 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bucki, F. J. Byfield, A. Kulakowska, M. E. McCormick, W. Drozdowski, Z. Namiot, T. Hartung, and P. A. Janmey Extracellular Gelsolin Binds Lipoteichoic Acid and Modulates Cellular Response to Proinflammatory Bacterial Wall Components J. Immunol., October 1, 2008; 181(7): 4936 - 4944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. DiNubile Plasma gelsolin: in search of its raison d'etre. Focus on "Modifications of cellular responses to lysophosphatidic acid and platelet-activating factor by plasma gelsolin" Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1240 - C1242. [Full Text] [PDF]
|
|
|
|
|
|
T. M. Osborn, C. Dahlgren, J. H. Hartwig, and T. P. Stossel Modifications of cellular responses to lysophosphatidic acid and platelet-activating factor by plasma gelsolin Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1323 - C1330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Marik, S. Pastores, D. Annane, R. Speich, C. Schmid, R. Stocker, H. Okamoto, M. J. DiNubile, K. P. Steinberg, L. D. Hudson, et al. Corticosteroids in ARDS. N. Engl. J. Med., July 20, 2006; 355(3): 316 - 317. [Full Text] [PDF]
|
|
|
|
 |
|
 U. Meier, O. Gressner, F. Lammert, and A. M. Gressner Gc-Globulin: Roles in Response to Injury Clin. Chem., July 1, 2006; 52(7): 1247 - 1253. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
