Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion

Patrick C. Hines, Qin Zen, Sharran N. Burney, Deborah A. Shea, Kenneth Ataga, Eugene P. Orringer, Marilyn J. Telen, Leslie V. Parise

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

The vasoocclusive crisis is the major clinical feature of sickle cell anemia, which is believed to be initiated or sustained by sickle (SS) red blood cell (RBC) adhesion to the vascular wall- SS RBCs, but not unaffected (AA) RBCs, adhere avidly to multiple components of the vascular wall, including laminin. Here we report a novel role for epinephrine and cyclic adenosine monophosphate (cAMP) in the regulation of human SS RBC adhesiveness via the laminin receptor, basal cell adhesion molecule/Lutheran (BCAM/Lu). Our data demonstrate that peripheral SS RBCs contain greater than 4-fold more cAMP than AA RBCs under basal conditions. Forskolin or the stress mediator epinephrine further elevates cAMP in SS RBCs and increases adhesion of SS RBCs to laminin in a protein kinase A (PKA)-dependent manner, with the low-density population being the most responsive- Epinephrine-stimulated adhesion to laminin; mediated primarily via the β2-adrenergic receptor, occurred in SS RBC samples from 46% of patients and was blocked by recombinant, soluble BCAM/Lu, implicating this receptor as a target of cAMP signaling. Thus, these studies demonstrate a novel, rapid regulation of SS RBC adhesion by a cAMP-dependent pathway and suggest that components of this pathway, particularly PKA, the β2-adrenergic receptor, and BCAM/Lu, should be further explored as potential therapeutic targets to inhibit SS RBC adhesion.

Original languageEnglish (US)
Pages (from-to)3281-3287
Number of pages7
JournalBlood
Volume101
Issue number8
DOIs
StatePublished - Apr 15 2003
Externally publishedYes

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Cell adhesion
Cell Adhesion Molecules
Cell Adhesion
Cyclic AMP
Epinephrine
Blood
Erythrocytes
Chemical activation
Laminin
Cyclic AMP-Dependent Protein Kinases
Adrenergic Receptors
Blood Vessels
Adhesion
Laminin Receptors
Adhesiveness
Sickle Cell Anemia
Colforsin
Population Density

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Hines, P. C., Zen, Q., Burney, S. N., Shea, D. A., Ataga, K., Orringer, E. P., ... Parise, L. V. (2003). Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion. Blood, 101(8), 3281-3287. https://doi.org/10.1182/blood-2001-12-0289

Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion. / Hines, Patrick C.; Zen, Qin; Burney, Sharran N.; Shea, Deborah A.; Ataga, Kenneth; Orringer, Eugene P.; Telen, Marilyn J.; Parise, Leslie V.

In: Blood, Vol. 101, No. 8, 15.04.2003, p. 3281-3287.

Research output: Contribution to journalArticle

Hines, PC, Zen, Q, Burney, SN, Shea, DA, Ataga, K, Orringer, EP, Telen, MJ & Parise, LV 2003, 'Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion', Blood, vol. 101, no. 8, pp. 3281-3287. https://doi.org/10.1182/blood-2001-12-0289
Hines, Patrick C. ; Zen, Qin ; Burney, Sharran N. ; Shea, Deborah A. ; Ataga, Kenneth ; Orringer, Eugene P. ; Telen, Marilyn J. ; Parise, Leslie V. / Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion. In: Blood. 2003 ; Vol. 101, No. 8. pp. 3281-3287.
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