Interleukin-3 and Flt3-ligand induce adhesion of Baf3/Flt3 precursor B- lymphoid cells to fibronectin via activation of VLA-4 and VLA-5

Hirohiko Shibayama, Naoyuki Anzai, Alec Ritchie, Shuli Zhang, Charlie Mantel, Hal E. Broxmeyer

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Adhesion of hematopoietic cells to extracellular matrix components is important for blood cell development. However, little is known regarding the potential influence of IL-3 on this process for precursor B cells and Flt3- ligand has not yet been implicated in induction of adhesion of any blood cell types to extracellular matrix components. Therefore, we examined the characteristics of cytokine-induced cell adhesion to fibronectin (FN), using as a model the murine precursor B cell line, Baf3, a factor-dependent cell line requiring IL-3 for both growth and survival. Since factor-dependent hematopoietic cell lines expressing Flt3 receptor are extremely rare, we also studied Baf3/Flt3, a subline of Baf3 transduced with the Flt3 receptor gene. IL-3 induced adhesion of Baf3 and Baf3/Flt3 cells to FN, while Flt3-ligand induced adhesion of Baf3/Flt3 cells only. Whereas both Baf3 and Baf3/Flt3 cells expressed VLA-4 and -5 integrins as FN receptors, expression levels of VLA-4 and -5 were not affected by IL-3 or Flt3-ligand treatment. However, blocking experiments using anti-integrin antibodies showed that cytokine- induced adhesion of cells depended on both VLA-4 and -5 suggesting that IL-3 and Flt3-ligand activated these integrins. PI-3 kinase inhibitor wortmannin, PKC inhibitor H-7, or PKA inhibitor HA1004 did not suppress adhesion induced by IL-3 or Flt3-ligand; in contrast, PLC inhibitor U-73122 did suppress adhesion, suggesting the possibility that PLC, but not PI-3 kinase, PKC, or PKA, may be involved in this process. Since it is known that IL-3 and Flt3- ligand receptors are expressed on precursor B cells, and these receptors are downregulated during B cell maturation of primary cells, the induction of precursor B cell adhesion to FN by IL-3 and Flt3-ligand may contribute a mechanism by which precursor B cells adhere to bone marrow stroma, thereby influencing their development.

Original languageEnglish (US)
Pages (from-to)27-33
Number of pages7
JournalCellular Immunology
Volume187
Issue number1
DOIs
StatePublished - Jul 10 1998

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Keywords

  • Adhesion
  • Fibronectin
  • Flt3-ligand
  • IL-3, inside-out signaling
  • Precursor B cell

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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