H. Shibayama et al., INTERLEUKIN-3 AND FLT3-LIGAND INDUCE ADHESION OF BAF3 FLT3 PRECURSOR B-LYMPHOID CELLS TO FIBRONECTIN VIA ACTIVATION OF VLA-4 AND VLA-5/, Cellular immunology (Print), 187(1), 1998, pp. 27-33
Adhesion of hematopoietic cells to extracellular matrix components is
important for blood cell development. However, little is known regardi
ng the potential influence of IL-3 on this process for precursor B cel
ls and Flt3-ligand has not yet been implicated in induction of adhesio
n of any blood cell types to extracellular matrix components, Therefor
e, we examined the characteristics of cytokine-induced cell adhesion t
o 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 expre
ssed 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 cytoki
ne-induced adhesion of cells depended on both VLA-4 and -5 suggesting
that IL-3 and Flt3-ligand activated these integrins. PI-3 kinase inhib
itor wortmannin, PKC inhibitor H-7, or PKA inhibitor HA1004 did not su
ppress adhesion induced by IL-3 or Flt3-ligand; in contrast, PLC inhib
itor U-73122 did suppress adhesion, suggesting the possibility that PL
C, 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 cel
l maturation of primary cells, the induction of precursor B cell adhes
ion to FN by IL-3 and Flt3-ligand may contribute a mechanism by which
precursor B cells adhere to bone marrow stroma, thereby influencing th
eir development. (C) 1998 Academic Press.