Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 31 July 1987:
Vol. 237. no. 4814, pp. 500 - 506
DOI: 10.1126/science.3603036
Prev | Table of Contents | Next

Articles

Science, Vol 237, Issue 4814, 500-506
Copyright © 1987 by American Association for the Advancement of Science

articles

Delay time of hemoglobin S polymerization prevents most cells from sickling in vivo

A Mozzarelli, J Hofrichter, and WA Eaton

A laser photolysis technique has been developed to assess the quantitative significance of the delay time of hemoglobin S gelation to the pathophysiology of sickle cell disease. Changes in the saturation of hemoglobin S with carbon monoxide produced by varying the intensity of a photolytic laser beam were used to simulate changes in the saturation of oxyhemoglobin S produced by variations in oxygen pressure. The presence of polymer at steady-state saturation with carbon monoxide was determined by measurement of the kinetics of gelation after complete photodissociation. The kinetics are a very sensitive probe for polymer since small amounts of polymerized hemoglobin increase the rate of nucleation sufficiently to eliminate the delay period. First, the equilibrium gelation properties of partially photodissociated carbonmonoxyhemoglobin S were shown to be the same as partially oxygenated hemoglobin S, and the method was then used to determine the effect of saturation on the formation and disappearance of polymers in individual sickle cells. The saturation at which polymers first formed upon deoxygenation was much lower than the saturation at which polymers disappeared upon reoxygenation. The results indicate that at venous saturations with oxygen, gelation takes place in most cells at equilibrium, but is prevented from occurring in vivo because the delay times are sufficiently long that most cells return to the lungs and are reoxygenated before polymerization has begun.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A Novel High-Throughput Screening Assay for Sickle Cell Disease Drug Discovery.
E. Pais, J. S. Cambridge, C. S. Johnson, H. J. Meiselman, T. C. Fisher, and T. Alexy (2009)
J Biomol Screen 14, 330-336
   Abstract »    PDF »
Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia.
K. I. Ataga, W. R. Smith, L. M. De Castro, P. Swerdlow, Y. Saunthararajah, O. Castro, E. Vichinsky, A. Kutlar, E. P. Orringer, G. C. Rigdon, et al. (2008)
Blood 111, 3991-3997
   Abstract »    Full Text »    PDF »
Sickle cell vasoocclusion and rescue in a microfluidic device.
J. M. Higgins, D. T. Eddington, S. N. Bhatia, and L. Mahadevan (2007)
PNAS 104, 20496-20500
   Abstract »    Full Text »    PDF »
In vivo red blood cell sickling and mechanism of recovery in whiting, Merlangius merlangus.
P. Koldkjaer and M. Berenbrink (2007)
J. Exp. Biol. 210, 3451-3460
   Abstract »    Full Text »    PDF »
Activated polymorphonuclear cells increase sickle red blood cell retention in lung: role of phospholipids.
J. Haynes Jr. and B. Obiako (2002)
Am J Physiol Heart Circ Physiol 282, H122-H130
   Abstract »    Full Text »    PDF »
Modulation of Gardos channel activity by cytokines in sickle erythrocytes.
A. Rivera, P. Jarolim, and C. Brugnara (2002)
Blood 99, 357-363
   Abstract »    Full Text »    PDF »
Oxygen binding by single red blood cells from the red-eared turtle Trachemys scripta.
S. Frische, S. Bruno, A. Fago, R. E. Weber, and A. Mozzarelli (2001)
J Appl Physiol 90, 1679-1684
   Abstract »    Full Text »    PDF »
Sickle Cell Adhesion to Laminin: Potential Role for the alpha 5 Chain.
S. P. Lee, M. L. Cunningham, P. C. Hines, C. C. Joneckis, E. P. Orringer, and L. V. Parise (1998)
Blood 92, 2951-2958
   Abstract »    Full Text »    PDF »
cDNA Cloning and Functional Characterization of the Mouse Ca2+-gated K+ Channel, mIK1. ROLES IN REGULATORY VOLUME DECREASE AND ERYTHROID DIFFERENTIATION.
D. H. Vandorpe, B. E. Shmukler, L. Jiang, B. Lim, J. Maylie, J. P. Adelman, L. de Franceschi, M. D. Cappellini, C. Brugnara, and S. L. Alper (1998)
J. Biol. Chem. 273, 21542-21553
   Abstract »    Full Text »    PDF »
Endothelial Cells in Physiology and in the Pathophysiology of Vascular Disorders.
D. B. Cines, E. S. Pollak, C. A. Buck, J. Loscalzo, G. A. Zimmerman, R. P. McEver, J. S. Pober, T. M. Wick, B. A. Konkle, B. S. Schwartz, et al. (1998)
Blood 91, 3527-3561
   Full Text »    PDF »
Intracellular Hemoglobin S Polymerization and the Clinical Severity of Sickle Cell Anemia.
W. N. Poillon, B. C. Kim, and O. Castro (1998)
Blood 91, 1777-1783
   Abstract »    Full Text »    PDF »
Pathogenesis and Treatment of Sickle Cell Disease.
H. F. Bunn (1997)
N. Engl. J. Med. 337, 762-769
   Full Text »    PDF »
Effect of Hemoglobin Concentration on Nucleation and Polymer Formation in Sickle Red Blood Cells.
J. D. Corbett, W. E. Mickols, and M. F. Maestre (1995)
J. Biol. Chem. 270, 2708-2715
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)