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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2009-8-12
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pubmed:abstractText |
We reported that complement (C) becomes activated and cleaved in bone marrow during preconditioning for hematopoietic transplantation and the third C component (C3) cleavage fragments, C3a and (desArg)C3a, increase responsiveness of hematopoietic stem/progenitor cells (HSPCs) to stromal-derived factor-1 (SDF-1). We also showed that this homing-promoting effect is not C3a receptor (C3aR) dependent. Herein, we report our new observation that transplantation of C3aR(-/-) HSPCs into lethally irradiated recipients results in: (1) approximately 5-7 day delay in recovery of platelets and leukocytes; (2) decrease in formation of day 12 colony-forming units-spleen; and (3) decrease in the number of donor-derived CFU-granulocyte-macrophage progenitors detectable in the bone marrow cavities at day 16 after transplantation. In agreement with the murine data, blockage of C3aR on human umbilical cord blood CD34(+) cells by C3aR antagonist SB290157 impairs their engraftment in non-obese diabetic/severe combined immunodeficient mice. However, HSPCs from C3aR(-/-) mice stimulated by C3a still better responded to SDF-1 gradient, after exposure to C3a, they secrete less matrix metalloprotease-9 and show impaired adhesion to stroma cells. We conclude that C3a, in addition to enhancing responsiveness of HSPCs to SDF-1 gradient in a C3aR independent manner, may also directly modulate HSPC homing by augmenting C3aR-mediated secretion of matrix metalloprotease-9 and cell adhesion.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-10545519,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-10828007,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-11063876,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-11104786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-11154207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-11287977,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-11297706,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-11588037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-12444150,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-12511407,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-12540846,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-12690289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-1360268,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-1379610,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-14604969,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-15284858,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-15890683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-15990859,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-16148115,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-16840734,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-16863905,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-16893063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-17053451,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-17972941,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-19025113,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-3048487,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-6214588,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-7568190,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-8600394,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19357704-9680357
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1476-5551
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1455-61
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pubmed:dateRevised |
2010-12-17
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pubmed:meshHeading |
pubmed-meshheading:19357704-Animals,
pubmed-meshheading:19357704-Bone Marrow,
pubmed-meshheading:19357704-Cell Adhesion,
pubmed-meshheading:19357704-Cell Movement,
pubmed-meshheading:19357704-Colony-Forming Units Assay,
pubmed-meshheading:19357704-Complement C3a,
pubmed-meshheading:19357704-Fetal Blood,
pubmed-meshheading:19357704-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:19357704-Hematopoietic Stem Cells,
pubmed-meshheading:19357704-Humans,
pubmed-meshheading:19357704-Immunologic Deficiency Syndromes,
pubmed-meshheading:19357704-Matrix Metalloproteinase 9,
pubmed-meshheading:19357704-Mice,
pubmed-meshheading:19357704-Mice, Inbred BALB C,
pubmed-meshheading:19357704-Mice, Inbred NOD,
pubmed-meshheading:19357704-Mice, Knockout,
pubmed-meshheading:19357704-Mice, SCID,
pubmed-meshheading:19357704-Radiation Chimera,
pubmed-meshheading:19357704-Receptors, Complement,
pubmed-meshheading:19357704-Transplantation, Heterologous
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pubmed:year |
2009
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pubmed:articleTitle |
Defective engraftment of C3aR-/- hematopoietic stem progenitor cells shows a novel role of the C3a-C3aR axis in bone marrow homing.
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pubmed:affiliation |
Stem Cell Biology Program at the James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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