Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU

Meghan M. Murphy, Mohamed A. Zayed, Allyson Evans, Carol E. Parker, Kenneth Ataga, Marilyn J. Telen, Leslie V. Parise

Research output: Contribution to journalArticle

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Abstract

Vaso-occlusion is a hallmark of sickle cell disease. Agonist-induced activation of sickle red blood cells (SS RBCs) promotes their adhesion to vascular proteins, potentially contributing to vasoocclusion. Previously, we described a cyclic adenosine monophosphate (cAMP)-dependent increase in SS RBC adhesion to laminin. Here, we investigated whether Rap1, a small guanosine triphosphatase (GTPase) known to promote integrin-mediated adhesion in other cells, was involved in this signaling pathway. We found that agonists known to induce cAMP signaling promoted the GTP-bound, active state of Rap1 in SS RBCs. The cAMP-dependent exchange factor Epac (exchange protein directly activated by cAMP) is a likely upstream activator of Rap1, since Epac is present in these cells and the Epac-specific cAMP analog 8CPT-2-Me (8-(4-cholorophenylthio)- 2′-O-methyl-cAMP) activated Rap1 and promoted SS RBC adhesion to laminin. This 8CPT-2-Me-stimulated adhesion was integrin independent, since it was insensitive to RGD peptide or antibodies against the only known integrin on SS RBCs, α4β1. However, this adhesion was completely inhibited by either a soluble version of basal cell adhesion molecule/Lutheran (BCAM/LU) or a BCAM/LU adhesion-blocking antibody. Surprisingly, 8CPT-2-Me-activated Rap1 did not promote SS RBC adhesion to a known α4β1 ligand, vascular cell adhesion molecule 1 (VCAM-1). These results demonstrate that Epac-induced Rap1 activation in SS RBCs promotes BCAM/LU-mediated adhesion to laminin. Thus, Epac-mediated Rap1 activation may represent an important signaling pathway for promoting SS RBC adhesion.

Original languageEnglish (US)
Pages (from-to)3322-3329
Number of pages8
JournalBlood
Volume105
Issue number8
DOIs
StatePublished - Apr 15 2005

Fingerprint

Cell adhesion
Cell Adhesion Molecules
Laminin
Cell Adhesion
Blood
Cyclic AMP
Adhesion
Erythrocytes
Integrins
Proteins
Chemical activation
Blocking Antibodies
Vascular Cell Adhesion Molecule-1
Guanosine
Sickle Cell Anemia
Adenosine Monophosphate
Guanosine Triphosphate
Blood Vessels
Ligands
Antibodies

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Murphy, M. M., Zayed, M. A., Evans, A., Parker, C. E., Ataga, K., Telen, M. J., & Parise, L. V. (2005). Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU. Blood, 105(8), 3322-3329. https://doi.org/10.1182/blood-2004-07-2881

Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU. / Murphy, Meghan M.; Zayed, Mohamed A.; Evans, Allyson; Parker, Carol E.; Ataga, Kenneth; Telen, Marilyn J.; Parise, Leslie V.

In: Blood, Vol. 105, No. 8, 15.04.2005, p. 3322-3329.

Research output: Contribution to journalArticle

Murphy, MM, Zayed, MA, Evans, A, Parker, CE, Ataga, K, Telen, MJ & Parise, LV 2005, 'Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU', Blood, vol. 105, no. 8, pp. 3322-3329. https://doi.org/10.1182/blood-2004-07-2881
Murphy MM, Zayed MA, Evans A, Parker CE, Ataga K, Telen MJ et al. Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU. Blood. 2005 Apr 15;105(8):3322-3329. https://doi.org/10.1182/blood-2004-07-2881
Murphy, Meghan M. ; Zayed, Mohamed A. ; Evans, Allyson ; Parker, Carol E. ; Ataga, Kenneth ; Telen, Marilyn J. ; Parise, Leslie V. / Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU. In: Blood. 2005 ; Vol. 105, No. 8. pp. 3322-3329.
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