PMID- 10572085
OWN - NLM
STAT- MEDLINE
DCOM- 19991230
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 11
DP  - 1999 Dec 1
TI  - Differentiation stage-specific regulation of primitive human hematopoietic 
      progenitor cycling by exogenous and endogenous inhibitors in an in vivo model.
PG  - 3722-9
AB  - Nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice transplanted 
      with human cord blood or adult marrow cells and injected 6 weeks posttransplant 
      with 2 daily doses of transforming growth factor-beta(1) (TGF-beta(1)), monocyte 
      chemoattractant protein-1 (MCP-1), or a nonaggregating form of macrophage 
      inflammatory protein-1alpha (MIP-1alpha) showed unique patterns of inhibition of 
      human progenitor proliferation 1 day later. TGF-beta(1) was active on long-term 
      culture initiating cells (LTC-IC) and on primitive erythroid and granulopoietic 
      colony-forming cells (HPP-CFC), but had no effect on mature CFC. MCP-1 inhibited 
      the cycling of both types of HPP-CFC but not LTC-IC. MIP-1alpha did not inhibit 
      either LTC-IC or granulopoietic HPP-CFC but was active on erythroid HPP-CFC and 
      mature granulopoietic CFC. All of these responses were independent of the source 
      of human cells transplanted. LTC-IC of either human cord blood or adult marrow 
      origin continue to proliferate in NOD/SCID mice for many weeks, although the 
      turnover of all types of human CFC in mice transplanted with adult human marrow 
      (but not cord blood) is downregulated after 6 weeks. Interestingly, 
      administration of either MIP-1beta, an antagonist of both MIP-1alpha and MCP-1 or 
      MCP-1(9-76), an antagonist of MCP-1 (and MCP-2 and MCP-3), into mice in which 
      human marrow-derived CFC had become quiescent, caused the rapid reactivation of 
      these progenitors in vivo. These results provide the first definition of 
      stage-specific inhibitors of human hematopoietic progenitor cell cycling in vivo. 
      In addition they show that endogenous chemokines can contribute to late graft 
      failure, which can be reversed by the administration of specific antagonists.
FAU - Cashman, J D
AU  - Cashman JD
AD  - Department of Medical Genetics, University of British Columbia, Vancouver, 
      Canada.
FAU - Clark-Lewis, I
AU  - Clark-Lewis I
FAU - Eaves, A C
AU  - Eaves AC
FAU - Eaves, C J
AU  - Eaves CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Cell Lineage/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/*pharmacology
MH  - Chemokine CCL3
MH  - Chemokine CCL4
MH  - *Hematopoiesis/drug effects
MH  - Hematopoietic Stem Cells/*cytology/*drug effects
MH  - Humans
MH  - Macrophage Inflammatory Proteins/*pharmacology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Transforming Growth Factor beta/*pharmacology
EDAT- 1999/11/26 00:00
MHDA- 1999/11/26 00:01
CRDT- 1999/11/26 00:00
PHST- 1999/11/26 00:00 [pubmed]
PHST- 1999/11/26 00:01 [medline]
PHST- 1999/11/26 00:00 [entrez]
AID - S0006-4971(20)36687-8 [pii]
PST - ppublish
SO  - Blood. 1999 Dec 1;94(11):3722-9.