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The Complement Split Products C3a and C5a are potent Activators of Mesenchymal Stem Cells
Author(s) -
Schraufstatter Ingrid,
Discipio Richard,
Khaldoyanidi Sophia
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1030.13
Subject(s) - anaphylatoxin , mesenchymal stem cell , c5a receptor , microbiology and biotechnology , complement system , phosphorylation , biology , chemotaxis , receptor , stem cell , immunology , chemistry , immune system , biochemistry
It is known that mesenchymal stem cells (MSC) are recruited to sites of tissue injury to fulfill their repair function. It is also known that there is complement activation, wherever there is tissue injury. We therefore determined the effect of the complement split products C3a and C5a on MSC. FACS analysis indicated that human bone marrow‐derived MSCs express cell‐surface C3a receptors (C3aR) and C5a receptors (C5aR). Both C3a and C5a induced chemotaxis of MSCs in a dose dependent fashion. Specific C3aR and C5aR inhibitors blocked the chemotactic response as did pertussis toxin, indicating that the response was mediated by the known anaphylatoxin receptors in a Gi activation‐dependent fashion. While C5a causes prolonged activation of many cell types, the response to C3a is generally transient and weak. However, in MSCs both C3a and C5a caused prolonged ERK1/2 and Akt phosphorylation. Phospho‐Akt and phospho‐ERK1/2 were translocated to the nucleus with both stimuli, which was associated with subsequent phosphorylation of the transcription factor Elk. More surprisingly, the C3aR itself was translocated to the nucleus in C3a‐stimulated MSCs. Since nuclear translocation of G‐protein coupled receptors has been shown to induce long‐term effects including transcriptional activation, this novel observation implies that C3a exerts far reaching consequences on MSC biology. The prolonged activation of C3aRs and to a lesser degree of C5aRs was associated with increased expression of several angiogenic factors in MSC including VEGF, bFGF and IL‐8. These results suggest that C3a and C5a present in injured tissues contribute to the recruitment of MSC and that means of activating the C3aR or C5aR on MSC could improve their ischemic repair potential, which would be more attractive for C3a, which lacks the inflammatory action of C5a.