CHRONIC NEUTROPENIA - A NEW CANINE MODEL INDUCED BY HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR

被引:97
作者
HAMMOND, WP
CSIBA, E
CANIN, A
HOCKMAN, H
SOUZA, LM
LAYTON, JE
DALE, DC
机构
[1] AMGEN INC,THOUSAND OAKS,CA 91320
[2] LUDWIG INST CANC RES,MELBOURNE 3050,AUSTRALIA
关键词
IMMUNOGLOBULIN; INVITRO CULTURE; INVIVO TREATMENT;
D O I
10.1172/JCI115049
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Normal dogs were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 10-mu-g/day for 30 d, which caused an initial neutrophilia, followed by a prolonged period of chronic neutropenia. A control dog treated with recombinant canine G-CSF (rcG-CSF) showed persistent neutrophilia over 3 mo. Serum from digs during neutropenia contained an antibody to the rhG-CSF, which neutralized the stimulatory effects of both rhG-CSF and rcG-CSF on dog marrow neutrophilic progenitor cell growth and on NFS-60 cell proliferation. 4 mo after discontinuation of rhG-CSF, the dogs' neutrophil counts returned to the normal range. Rechallenge wit the rhG-CSF re-induced severe neutropenia in 1 wk. Neutropenia was transferred by plasma infusion from a neutropenic dog to a previously normal dog. These data suggest that human rhG-CSF immunizes normal dogs and thereby induces neutralization of endogenous canine G-CSF and neutropenia. This model system should allow more precise definition of the in vivo role of G-CSF.
引用
收藏
页码:704 / 710
页数:7
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