The rate of apoptosis in post mitotic neutrophil precursors of normal and neutropenic humans

被引:32
作者
Mackey, MC
Aprikyan, AAG
Dale, DC
机构
[1] McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada
[2] McGill Univ, Dept Math & Phys, Montreal, PQ H3G 1Y6, Canada
[3] McGill Univ, Ctr Nonlinear Dynam, Montreal, PQ H3G 1Y6, Canada
[4] Univ Washington, Div Hematol, Seattle, WA 98195 USA
[5] Univ Washington, Dept Med, Seattle, WA 98195 USA
关键词
D O I
10.1046/j.1365-2184.2003.00251.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Using data on the fraction of post-mitotic neutrophil precursors (CD15(+) cells) displaying positive markers for apoptosis in 12 normal humans, and a simple mathematical model, we have estimated the apoptotic rate to be about 0.28/day in this compartment. This implies that the influx of myelocytes into the post-mitotic compartment exceeds twice the granulocyte turnover rate (GTR), and that about 55% of the cells entering this compartment die before being released into the blood. The normal half life of apoptotic post-mitotic neutrophil precursors is calculated to be 10.4 h. Comparable calculations for patients indicate apoptosis rates in the post-mitotic compartment of about 17 times normal for one myelokathexis patient and rates of about 13 times normal for the one cyclical neutropenic patient and two severe congenital neutropenic patients. The estimated half life for apoptotic post-mitotic neutrophil precursors in the myelokathexis patient was about 0.4 h, 1.4 h in the cyclical neutropenia patient, and about 0.6 h in the severe congenital neutropenic patients.
引用
收藏
页码:27 / 34
页数:8
相关论文
共 31 条
[1]   In vivo kinetics of murine hemopoietic stem cells [J].
Abkowitz, JL ;
Golinelli, D ;
Harrison, DE ;
Guttorp, P .
BLOOD, 2000, 96 (10) :3399-3405
[2]   Evidence that hematopoiesis may be a stochastic process in vivo [J].
Abkowitz, JL ;
Catlin, SN ;
Guttorp, P .
NATURE MEDICINE, 1996, 2 (02) :190-197
[3]   Activation of the cyclin D1 gene by the EPA-associated protein p300 through AP-1 inhibits cellular apoptosis [J].
Albanese, C ;
D'Amico, M ;
Reutens, AT ;
Fu, MF ;
Watanabe, G ;
Lee, RJ ;
Kitsis, RN ;
Henglein, B ;
Avantaggiati, M ;
Somasundaram, K ;
Thimmapaya, B ;
Pestell, RG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (48) :34186-34195
[4]   Flow cytometry using annexin V can detect early apoptosis in peripheral blood stem cell harvests from patients with leukaemia and lymphoma [J].
Anthony, RS ;
McKelvie, ND ;
Cunningham, AJ ;
Craig, JIO ;
Rogers, SY ;
Parker, AC .
BONE MARROW TRANSPLANTATION, 1998, 21 (05) :441-446
[5]   Myelokathexis, a congenital disorder of severe neutropenia characterized by accelerated apoptosis and defective expression of bcl-x in neutrophil precursors [J].
Aprikyan, AAG ;
Liles, WC ;
Park, JR ;
Jonas, M ;
Chi, EY ;
Dale, DC .
BLOOD, 2000, 95 (01) :320-327
[6]   RETRACTED: Impaired survival of bone marrow hematopoietic progenitor cells in cyclic neutropenia (Retracted Article) [J].
Aprikyan, AAG ;
Liles, WC ;
Rodger, E ;
Jonas, M ;
Chi, EY ;
Dale, DC .
BLOOD, 2001, 97 (01) :147-153
[7]   AGE-STRUCTURED AND 2-DELAY MODELS FOR ERYTHROPOIESIS [J].
BELAIR, J ;
MACKEY, MC ;
MAHAFFY, JM .
MATHEMATICAL BIOSCIENCES, 1995, 128 (1-2) :317-346
[8]  
Bradford GB, 1997, EXP HEMATOL, V25, P445
[9]  
CHATTA GS, 1994, BLOOD, V84, P2923
[10]   In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells [J].
Cheshier, SP ;
Morrison, SJ ;
Liao, XS ;
Weissman, IL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (06) :3120-3125