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Blood, Vol. 93 No. 10 (May 15), 1999:
pp. 3317-3326
Modulation of Integrin Function in Hematopoietic Progenitor Cells by
CD43 Engagement: Possible Involvement of Protein Tyrosine Kinase
and Phospholipase C-
Naoyuki Anzai,
Akihiko Gotoh,
Hirohiko Shibayama, and
Hal E. Broxmeyer
From the Departments of Microbiology/Immunology, Medicine, and the
Walther Oncology Center, Indiana University School of Medicine,
Indianapolis, IN.
Attachment of cells to extracellular matrix components is critical
for the regulation of hematopoiesis. CD43 is a mucin-like transmembrane
sialoglycoprotein expressed on the surface of almost all hematopoietic
cells. A highly extended structure of extracellular mucin with negative
charge may function as a repulsive barrier to hematopoietic cells.
However, some investigators have shown that CD43 has proadhesive
properties, and engagement of CD43 has been reported to upregulate
integrin-mediated cell adhesion in T cells. We found that cross-linking
of CD43 with monoclonal antibodies (MoAbs) enhanced integrin  4 1
(very late antigen [VLA]-4) and 5 1 (VLA-5)-dependent adhesion
of human cord blood CD34+ cells to fibronectin.
CD34+ CD38hi, but not
CD34+CD38 /low cells responded
significantly to the stimulus, suggesting that committed, but not stem
and more immature progenitors are sensitive to CD43-mediated activation
of integrin. To elucidate the molecular mechanism leading to integrin
activation, we used the growth factor-dependent cell line MO7e.
Cross-linking of CD43 induced tyrosine phosphorylation of several
intracellular molecules including the protein tyrosine kinase Syk, the
proto-oncogene product Cbl, and phospholipase C (PLC)- 2 in MO7e
cells. Moreover, protein tyrosine kinase inhibitor herbimycin A and PLC
inhibitor U73122 both blocked CD43-induced enhancement of adhesion to
fibronectin. These results indicate that signals mediated through CD43
may increase integrin affinity to fibronectin via a pathway dependent
on protein tyrosine kinase and PLC- activation in hematopoietic progenitors.
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