Details

Autor(en) / Beteiligte

• Marquez‐Curtis, Leah
• Jalili, Ali
• Deiteren, Kathleen
• Shirvaikar, Neeta
• Lambeir, Anne‐Marie
• Janowska‐Wieczorek, Anna

Titel

Carboxypeptidase M Expressed by Human Bone Marrow Cells Cleaves the C‐Terminal Lysine of Stromal Cell‐Derived Factor‐1α: Another Player in Hematopoietic Stem/Progenitor Cell Mobilization?

Ist Teil von

• Stem cells (Dayton, Ohio), 2008-05, Vol.26 (5), p.1211-1220

Ort / Verlag

Bristol: John Wiley & Sons, Ltd

Erscheinungsjahr

2008

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Carboxypeptidase M (CPM) is a membrane‐bound zinc‐dependent protease that cleaves C‐terminal basic residues, such as arginine or lysine, from peptides/proteins. We examined whether CPM is expressed by hematopoietic and stromal cells and could degrade stromal cell‐derived factor (SDF)‐1α, a potent chemoattractant for hematopoietic stem/progenitor cells (HSPC). We found that (a) CPM transcript is expressed by bone marrow (BM) and mobilized peripheral blood CD34+ cells, myeloid, erythroid, and megakaryocytic cell progenitors, mononuclear cells (MNC), polymorphonuclear cells (PMN), and stromal cells, including mesenchymal stem cells; and that (b) granulocyte‐colony‐stimulating factor (G‐CSF) significantly increases its expression at the gene and protein levels in MNC and PMN. Moreover, we found that recombinant CPM cleaves full‐length SDF‐1α (1–68) rapidly, removing the C‐terminal lysine and yielding des‐lys SDF‐1α (1–67). We demonstrated that such CPM treatment of SDF‐1α reduced the in vitro chemotaxis of HSPC, which, however, was preserved when the CPM was exposed to the carboxypeptidase inhibitor dl‐2‐mercaptomethyl‐3‐guanidino‐ethylthiopropanoic acid. Thus, we present evidence that CPM is expressed by cells occurring in the BM microenvironment and that the mobilizing agent G‐CSF strongly upregulates it in MNC and PMN. We suggest that cleavage of the C‐terminal lysine residue of SDF‐1α by CPM leads to attenuated chemotactic responses and could facilitate G‐CSF‐induced mobilization of HSPC from BM to peripheral blood. Disclosure of potential conflicts of interest is found at the end of this article.