Fetal haemopoietic cells display enhanced migration across endothelium

Yong, Kwee; Fahey, Anne; Pahal, Gurmit S.; Linch, David C.; Pizzey, Arnold; Thomas, Nancy; Jauniaux, Eric; Kinnon, Christine; Thrasher, Adrian J.

doi:10.1046/j.1365-2141.2002.03273.x

Cited by 14 publications

(13 citation statements)

References 21 publications

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“…What is clear is that fetal/neonatal cells appear to cycle spontaneously at a higher rate than their adult counterparts. For example, a higher percentage of freshly isolated fetal CD34 ϩ hemopoietic stem cells appear to be in cycle compared with the adult CD34 ϩ population (32,33). This spontaneous proliferation is not limited to hemopoietic cells.…”

Section: Discussionmentioning

confidence: 99%

Murine Neonatal Lymphocytes Show Rapid Early Cell Cycle Entry and Cell Division

Adkins

Williamson

Guevara

et al. 2003

The Journal of Immunology

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Neonatal animals are highly susceptible to infectious agents. At least part of this susceptibility is due to the virtual absence of immunological memory in newborns. One of the hallmarks of memory is the rapidity of the response. We show in this study that neonates may make up for their lack of memory, at least in part, by the rapid entry of large proportions of naive lymphocytes into the cell cycle. Following activation, greater percentages of both CD4+ and CD8+ neonatal, as compared with adult, lymph node cells showed early cell cycle entry; this was assessed by propidium iodide staining, CFSE labeling profiles, [3H]thymidine uptake, and up-regulation of early activation markers. This rapid cycle entry was observed following polyclonal activation with anti-CD3 or with PMA and ionomycin and in both C57BL/6 and BALB/c mice. Stimulation with specific peptide also elicited more rapid proliferative responses from neonatal vs adult TCR transgenic CD4+ cells. In addition, more rapid cycle entry was observed in vivo, in lymphopenic RAG2−/− hosts. For both CD4+ and CD8+ cells, this phenomenon was observed out to 3 wk of life, although the differences between neonatal and adult cells became smaller with increasing time postbirth. These properties of peripheral neonatal T cells appeared to be inherited from their thymic precursors, because CD4+8− single-positive cells in the neonatal thymus also showed more rapid cycle entry, compared with their counterparts in the adult thymus. Interestingly, rapid early cycling was also observed among activated neonatal B cells, compared with adult B cells. Thus, early cell cycle entry by large proportions of cells may allow the naive lymphocyte population to efficiently mobilize responses against the broad range of pathogens first encountered in neonatal life.

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Section: Discussionmentioning

confidence: 99%

Murine Neonatal Lymphocytes Show Rapid Early Cell Cycle Entry and Cell Division

Adkins

Williamson

Guevara

et al. 2003

The Journal of Immunology

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“…41 They are implicated in migration of leukocytes, inflammatory responses and regulation of tumor growth, as well as hematopoiesis. [42][43][44] SDF1a and its receptor CXCR4 play important roles in migration of HSC from the fetal liver to the fetal BM 45,46 as well as in postnatal life. 47,48 In CML, chemotaxis towards SDF1a is impaired, 49,50 which may contribute to the premature release of leukemic progenitors from the BM into the circulation.…”

Section: Discussionmentioning

confidence: 99%

BCR/ABL-mediated downregulation of genes implicated in cell adhesion and motility leads to impaired migration toward CCR7 ligands CCL19 and CCL21 in primary BCR/ABL-positive cells

et al. 2005

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The mechanism underlying p210 BCR/ABL oncoprotein-mediated transformation in chronic myelogenous leukemia (CML) is not fully understood. We hypothesized that p210 BCR/ABL suppresses expression of genes which may explain at least some of the pathogenetic features of CML. A subtractive cDNA library was created between BCR/ABL-enhanced-green-fluorescentprotein (GFP)-transduced umbilical cord blood (UCB) CD34 þ cells and GFP-transduced UCB CD34 þ cells to identify genes whose expression is downregulated by p210 BCR/ABL . At least 100 genes were identified. We have confirmed for eight of these genes that expression was suppressed by quantitative realtime-RT-PCR (Q-RT-PCR) of additional p210 BCR/ABL -transduced CD34 þ UCB cells as well as primary early chronic phase (CP) bone marrow (BM) CML CD34 þ cells. Imatinib mesylate reversed downregulation of some genes, to approximately normal levels. Several of the genes are implicated in cell adhesion and motility, including L-selectin, intercellular adhesion molecule-1 (ICAM-1), and the chemokine receptor, CCR7, consistent with the known defect in adhesion and migration of CML cells. Compared with GFP UCB or normal (NL) BM CD34 þ cells, p210 UCB and CML CD34 þ cells migrated poorly towards the CCR7 ligands, CCL19 and CCL21, suggesting a possible role for CCR7 in the abnormal migratory behavior of CML CD34 þ cells.

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“…Whether this enhancement of motility brings the SDF-1/CXCR4 pathway into prominence is unclear. By the same vein, whether cells with inherent increase in motility, that is, fetal-liver cells or cord-blood HPCs, 55,56 follow the same hierarchy in pathway usage as cytokineincubated cells remains to be seen.…”

Section: Homing Of Cytokine-incubated Bm-hpcsmentioning

confidence: 99%

Hierarchy of molecular-pathway usage in bone marrow homing and its shift by cytokines

Bönig

Priestley

Papayannopoulou

2006

Blood

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Efficient bone marrow (BM) homing is a prerequisite for successful engraftment of transplanted hematopoietic cells (HPCs).Contradictory conclusions about the contribution of SDF-1/CXCR4 have clouded our understanding of its role within the molecular pathway cooperation needed for BM homing, particularly with the welldefined hierarchic network of adhesion molecules. In the present study we sought to unravel cooperative and compensatory molecular pathways guiding BM homing. Fresh BM-HPCs, rendered either SDF-1 unresponsive or Gi-signaling refractory, homed quite efficiently, because of compensation by ␣4-integrin interacting with VCAM-1. The contribution of SDF-1/CXCR4-or Gi-protein-mediated signals to BM homing became apparent after their blockade was combined with deletion of ␣4-integrin, leading to dramatic reduction in BM homing. Similar conclusions were revealed when VCAM-1-deficient hosts were used. IntroductionBone marrow (BM) homing and engraftment are sequential steps in hematopoietic reconstitution after transplantation. The molecular mechanisms of BM homing have been under investigation for several years, and a host of contributing molecular players have been described, including integrins and endothelial selectins with their respective ligands, CD44, complement, certain lipid mediators, and intracellular signaling molecules. [1][2][3][4][5][6][7][8][9] Recently, the chemokine SDF-1 and its receptor CXCR4 have garnered much interest because of their dominant role as a homing-defining molecule in several tissues. 10,11 SDF-1 is expressed by a wide variety of cells, including hematopoietic cells (HPCs) and BM stromal cells, and is displayed as cell-bound, extracellular matrix-bound, or in soluble form. It is greatly up-regulated in many tissues, including BM, by "stress," such as injury or irradiation. CXCR4 is expressed predominantly intracellularly in immature hematopoietic cells, where it can be rapidly surface-expressed via clathrin-coated pits, to function as SDF-1 receptor. 12 All known functions of SDF-1 (antiapoptosis, proliferation, adhesion, and migration) are mediated through binding to its receptor, CXCR4, which signals through Gi-protein second messengers. Downstream signals involve IP3 and PKC, 13 and, although a Gi-independent contribution of the Jak/Stat pathway to IP3 activation has been shown, in the absence of Gi-signaling Jak/Stat activation could not elicit functional SDF-1 downstream signaling events. [14][15][16] In contrast to its wellestablished and generally accepted role in BM retention of HPCs and in long-term maintenance of hematopoiesis, evidence of a role of SDF-1/CXCR4/Gi-protein-dependent signaling in BM homing is unsettled because of discrepant data. [17][18][19][20][21][22][23][24][25] The purpose of the experiments described here was to explore possible reasons for disparity in findings about the role of Gi-signals in BM homing and to further define hierarchic pathway usage in homing. Our data suggest that BM homing of immature HPCs is guided by cooperating molecules w...

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Fetal haemopoietic cells display enhanced migration across endothelium

Cited by 14 publications

References 21 publications

Murine Neonatal Lymphocytes Show Rapid Early Cell Cycle Entry and Cell Division

Murine Neonatal Lymphocytes Show Rapid Early Cell Cycle Entry and Cell Division

BCR/ABL-mediated downregulation of genes implicated in cell adhesion and motility leads to impaired migration toward CCR7 ligands CCL19 and CCL21 in primary BCR/ABL-positive cells

Hierarchy of molecular-pathway usage in bone marrow homing and its shift by cytokines

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