Activation of sickle red blood cell adhesion via integrin-associated protein/CD47-induced signal transduction

J. E. Brittain, K. J. Mlinar, C. S. Anderson, E. P. Orringer, L. V. Parise

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Peripheral human red blood cells (RBCs) are not generally known to become activated and adhesive in response to cell signaling. We show, however, that soluble thrombospondin via integrin-associated protein (IAP; CD47) increases the adhesiveness of sickle RBCs (SS RBCs) by activating signal transduction in the SS RBC. This stimulated adhesion requires occupancy of IAP and shear stress and is mediated by the activation of large G proteins and tyrosine kinases. Reticulocyte-enriched RBCs derived from sickle-cell disease (SCD) patients are most responsive to IAP-induced activation. These studies therefore establish peripheral SS RBCs as signaling cells that respond to a novel synergy between IAP-induced signal transduction and shear stress, suggesting new therapeutic targets in SCD.

Original languageEnglish (US)
Pages (from-to)1555-1562
Number of pages8
JournalJournal of Clinical Investigation
Volume107
Issue number12
DOIs
StatePublished - Jan 1 2001

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Cell Adhesion
Integrins
Signal Transduction
Erythrocytes
Proteins
Sickle Cell Anemia
Thrombospondins
Adhesiveness
Reticulocytes
GTP-Binding Proteins
Adhesives
Protein-Tyrosine Kinases

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Activation of sickle red blood cell adhesion via integrin-associated protein/CD47-induced signal transduction. / Brittain, J. E.; Mlinar, K. J.; Anderson, C. S.; Orringer, E. P.; Parise, L. V.

In: Journal of Clinical Investigation, Vol. 107, No. 12, 01.01.2001, p. 1555-1562.

Research output: Contribution to journalArticle

Brittain, J. E. ; Mlinar, K. J. ; Anderson, C. S. ; Orringer, E. P. ; Parise, L. V. / Activation of sickle red blood cell adhesion via integrin-associated protein/CD47-induced signal transduction. In: Journal of Clinical Investigation. 2001 ; Vol. 107, No. 12. pp. 1555-1562.
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