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EMAP II induces migration of EPC and monocytes via the chemokine receptor CXCR3
Author(s) -
Clauss Matthias,
Hou Yonghao,
Yoder Mervin,
Ingram David,
Petrache Irina,
Voswinckel Robert
Publication year - 2007
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.21.5.a379-h
Subject(s) - progenitor cell , endothelial progenitor cell , chemokine , chemokine receptor , microbiology and biotechnology , monocyte , receptor , chemotaxis , immunology , chemistry , biology , inflammation , stem cell , biochemistry
The recruitment of endothelial progenitor cells to the sites of ischemia has recently been suggested as a mechanism of tissue repair. Based on our previous finding that endothelial‐monocyte‐activating polypeptide II (EMAP II) is induced by hypoxia we addressed the hypothesis that EMAP II expression is required for recruiting highly proliferative late outgrowth endothelial progenitor cells (EPC), which express markers for endothelial cells but not macrophages. In cell culture experiments utilizing recombinant human EMAP II and EPC from cord blood, EMAP II induced a dose dependent migration and intracellular calcium mobilization in EPC. Functional blocking and binding studies indicated that these effects were mediated via the CXCR3 receptor. Interestingly, EMAP II–induced chemotaxis of cells of the monocyte/macrophage lineage were also CXCR3 receptor‐dependent. To investigate the role and mechanism of EMAP II‐mediated cell recruitment in vivo in the lung, we generated an alveolar type II cell‐specific tetracycline‐inducible EMAP II transgenic mouse. Upon tetracycline treatment, these mice had a robust EMAP II expression in the alveolar epithelium and secretion of EMAP II protein into the broncho alveolar lavage fluid. We suggest that this model will be helpful to evaluate the role of EMAP II‐mediated EPC and monocyte recruitment in lung injury and repair.