Poster abstracts

Poster number 50 submitted by Mary Forget

The potential for a specialized subset of cells, Tie2-Expressing monocytes, to regulate ischemic wound healing

Mary Forget (Molecular Cellular and Developmental Biology Graduate Program, Ohio State University), Tim Eubank (Pulmonary Division, Department of Internal Medicine, Ohio State University), Clay Marsh (Pulmonary Division, Department of Internal Medicine, Ohio State University)

Abstract:
Tie-2 is a Tyrosine Kinase Receptor with IgG and EFG domains. First described on vascular endothelial cells, activation of the Tie-2 receptor by its ligands, the Angiopoietins (Ang-1 and -2) modulate blood vessel growth and function. The binding of Ang-1 to Tie-2 induces stabilization of existing blood vessels while binding of Ang-2 destabilizes blood vessels and facilitates the sprouting of new vasculature. Recently, it has been shown that approximately seven percent of circulating CD14+/CD16+ human monocytes are Tie-2-expressing monocytes (TEMs). TEMs migrate toward Angiopoietin-2 as this subpopulation does not express CCR2, the receptor for MCP-1/CCL2, well-known to recruit monocytes. Recently discovered in solid tumors, TEMs reside in hypoxic regions peripherally to existing blood vessels, supporting the vasculature and promoting angiogenesis. Hypoxia has been shown to increase both the number of monocytes that express the Tie-2 receptor and the level of expression of Tie-2 on monocytes, possibly mobilizing more TEMs into in a supporting role from circulation. It is known that macrophages contribute to increased angiogenesis and we have shown previously that the polarity of these macrophages (M1 vs M2) can be regulated by the presence of growth factors such as granulocyte/macrophage colony-stimulating factor (GM-CSF). We previously elucidated a mechanism in which GM-CSF “re-educated” M2-type macrophages back into an M1 phenotype, leading to reduction in tumor angiogenesis. In this study, we show that treatment of Tie2-expressing monocytes with GM-CSF reduces the expression of the Tie-2 receptor which is up-regulated by hypoxia. In summary, the absence of Tie-2-expressing monocytes in hard-to-heel wounds may play a role in promoting an ischemic phenotype.

Keywords: monocyte, Tie2, Angiogenesis