Fibronectin bridges monocytes and reticulocytes via integrin α4β1

Julia E. Brittain, Christine M. Knoll, Kenneth Ataga, Eugene P. Orringer, Leslie V. Parise

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Leucocytes are emerging as critical determinants in the severity of the pathology associated with sickle cell disease (SCD) and recent studies have shown that they can bind to sickle red blood cells (SS RBCs). However, the mechanism of this interaction is unclear. The α4β1 integrin on monocytes and SS reticulocytes was found to mediate the interaction of these cells in in-vitro adhesion assays and in the blood of SCD patients. Plasma fibronectin (Fn), a ligand for α4β1, could link SS RBCs to monocytes, as peptides derived from both the Arg-Gly-Asp-Ser (RGDS) and CS-1 site in Fn disrupted the reticulocyte/monocyte interaction. It was further shown in whole blood that 70% of the interacting monocytes were also bound to platelets, suggesting the existence of multi-cellular aggregates in SCD. Platelet inclusion in these aggregates was mediated by a P-selectin/P-selectin glycoprotein ligand-1 interaction, which has been demonstrated to activate the monocyte. These results suggest a new model for understanding the mechanism of attachment of SS RBCs to monocytes and implicate the platelet as a component and contributor to potentially occlusive aggregates that circulate in the blood of SCD patients.

Original languageEnglish (US)
Pages (from-to)872-881
Number of pages10
JournalBritish Journal of Haematology
Volume141
Issue number6
DOIs
StatePublished - Jun 1 2008

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Reticulocytes
Fibronectins
Integrins
Monocytes
Sickle Cell Anemia
Blood Platelets
Blood Cells
arginyl-glycyl-aspartyl-serine
P-Selectin
Cell Communication
Leukocytes
Erythrocytes
Pathology
Ligands
Peptides

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Fibronectin bridges monocytes and reticulocytes via integrin α4β1. / Brittain, Julia E.; Knoll, Christine M.; Ataga, Kenneth; Orringer, Eugene P.; Parise, Leslie V.

In: British Journal of Haematology, Vol. 141, No. 6, 01.06.2008, p. 872-881.

Research output: Contribution to journalArticle

Brittain, Julia E. ; Knoll, Christine M. ; Ataga, Kenneth ; Orringer, Eugene P. ; Parise, Leslie V. / Fibronectin bridges monocytes and reticulocytes via integrin α4β1. In: British Journal of Haematology. 2008 ; Vol. 141, No. 6. pp. 872-881.
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