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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-03-0864.
Submitted March 19, 2002
Accepted July 23, 2002
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
Fujisaki Cell Center, Hayashibara Biochemical Labs Inc, Okayama, Japan
Kurashiki Medical Center, Okayama, Japan
* Corresponding author; email: fcch{at}hayashibara.co.jp.
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 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 culture, while 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 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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