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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-03-0864.
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Blood, 15 December 2002, Vol. 100, No. 13, pp. 4440-4445
HEMATOPOIESIS
CD45 tyrosine phosphatase inhibits erythroid differentiation of
umbilical cord blood CD34+ cells associated with selective
inactivation of Lyn
Akira Harashima,
Motoyuki Suzuki,
Ayumi Okochi,
Mayuko Yamamoto,
Yoshinobu Matsuo,
Ryuichi Motoda,
Tamotsu Yoshioka, and
Kunzo Orita
From the Fujisaki Cell Center, Hayashibara Biochemical
Labs, and the Kurashiki Medical Center, Kurashiki, Okayama,
Japan.
CD45 is a membrane-associated tyrosine phosphatase that
dephosphorylates Src family kinases and Janus kinases (JAKs). To
clarify the role of CD45 in hematopoietic differentiation, we examined the effects of anti-CD45 monoclonal antibody NU-LPAN on the
proliferation and differentiation of umbilical cord blood
CD34+ cells. NU-LPAN showed a prominent
inhibition of the proliferation of CD34+ cells induced by
the mouse bone marrow stromal cell line MS-5 or erythropoietin (EPO).
However, NU-LPAN did not affect the proliferation induced
by interleukin 3. NU-LPAN also inhibited MS-5-induced or
EPO-induced erythroid differentiation of CD34+ cells. The
cells stimulated with EPO in the presence of NU-LPAN morphologically showed differentiation arrest at the stage of basophilic erythroblasts after 11 days of culture, whereas the cells
treated with EPO without NU-LPAN differentiated into mature red blood cells. The Src family kinase Lyn and JAK2 were phosphorylated when erythroblasts obtained after 4 days of culture of
CD34+ cells in the presence of EPO were restimulated with
EPO. Overnight NU-LPAN treatment before addition of EPO
reduced the phosphorylation of Lyn but not that of JAK2.
Simultaneously, the enhancement of Lyn kinase activity after
restimulation with EPO was reduced by NU-LPAN treatment.
These results indicate selective inactivation of Lyn by CD45 activated
with NU-LPAN and could partly explain the inhibitory
mechanism on erythropoiesis exhibited by EPO. These findings suggest
that CD45 may play a pivotal role in erythropoiesis.
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