Cell cycle-dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity

Area of Science:

• Immunology
• Cell Biology
• Vascular Biology

Background:

• The receptors for angiostatic chemokines IFN-gamma-inducible protein of 10 kDa (IP-10) and monokine induced by IFN-gamma (Mig) on endothelial cells remain unidentified.
• The precise mechanisms by which these chemokines affect angiogenesis are not fully understood.

Purpose of the Study:

• To identify the endothelial cell receptor for IP-10 and Mig.
• To investigate the role of this receptor in endothelial cell proliferation and angiogenesis.

Main Methods:

• In situ hybridization and immunohistochemistry were used to detect CXC chemokine receptor 3 (CXCR3) expression in human tissues and microvascular endothelial cells.
• Primary cultures of human microvascular endothelial cells (HMVECs) were utilized to study CXCR3 expression and function.
• The effects of IP-10, Mig, and I-TAC on HMVEC proliferation were assessed in vitro, with and without an anti-CXCR3 antibody.

Main Results:

• CXC chemokine receptor 3 (CXCR3) was detected on a subset of microvascular endothelial cells in various human tissues.
• CXCR3 expression in primary human microvascular endothelial cells (HMVECs) was cell-cycle dependent, observed primarily in the S/G2-M phase.
• IP-10, Mig, and I-TAC inhibited HMVEC proliferation in vitro, an effect reversible by an anti-CXCR3 antibody.

Conclusions:

• This study provides definitive evidence for CXC chemokine receptor 3 (CXCR3) expression on human microvascular endothelial cells (HMVECs).
• The identified CXCR3 pathway offers potential therapeutic strategies for diseases where inhibiting angiogenesis is beneficial.