Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1.
Blood
; 101(10): 3784-93, 2003 May 15.
Article
em En
| MEDLINE
| ID: mdl-12511407
ABSTRACT
Complement has recently been implicated in developmental pathways and noninflammatory processes. The expression of various complement components and receptors has been shown in a wide range of circulating myeloid and lymphoid cells, but their role in normal hematopoiesis and stem cell homing has not yet been investigated. We report that normal human CD34(+) cells and lineage-differentiated hematopoietic progenitors express the complement anaphylatoxin C3a receptor (C3aR) and respond to C3a. Moreover, C3a, but not the biologically inactive desArg-C3a, induces calcium flux in these cells. Furthermore, we found that C3 is secreted by bone marrow stroma and that, although C3a does not influence directly the proliferation/survival of hematopoietic progenitors, it (1) potentiates the stromal cell-derived factor 1 (SDF-1)-dependent chemotaxis of human CD34(+) cells and lineage-committed myeloid, erythroid, and megakaryocytic progenitors; (2) primes SDF-1-dependent trans-Matrigel migration; and (3) stimulates matrix metalloproteinase-9 secretion and very late antigen 4 (VLA-4)-mediated adhesion to vascular cell adhesion molecule 1 (VCAM-1). Furthermore, we found that murine Sca-1(+) cells primed by C3a engrafted faster in lethally irradiated animals. These results indicate that normal human hematopoietic stem and progenitor cells express functional C3aR and that the C3aR-C3a axis sensitizes the responses of these cells to SDF-1 and thus may be involved in promoting their homing into the bone marrow via cross talk with the SDF-CXC chemokine receptor-4 (CXCR4) signaling axis. C3a is the first positive regulator of this axis to be identified.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células da Medula Óssea
/
Células-Tronco Hematopoéticas
/
Receptores de Complemento
/
Complemento C3a
/
Quimiotaxia
/
Antígeno de Macrófago 1
/
Células Estromais
/
Quimiocinas CXC
/
Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos