Differential expression and responsiveness of chemokine receptors (CXCR1–3) by human microvascular endothelial cells and umbilical vein endothelial cells

We recently reported, based on an RNase protection assay, that human umbilical vein endothelial cells did not express detectable mRNA for the interleukin 8 receptors CXCR1 and CXCR2

Rosalba Salcedo; James H. Resau; Douglas Halverson; Eric A. Hudson; Michael Dambach; Douglas Powell; Ken Wasserman; Joost J. Oppenheim

2002

Scholarcy highlights

  • The basis for the angiogenic effects of CXC chemokines such as interleukin 8 and for angiostatic chemokines such as interferon-inducible protein 10 has been difficult to assess
  • The data shows one representative field of four experiments. Calcium mobilization is another functional capability displayed by many chemokine receptors; we studied the capacity of IL-8 to induce calcium fluxes in human microvascular dermal endothelial cells
  • Our experiments indicated that IP-10, ITAC, and macrophage-derived interferon gamma-inducible chemokine per se can induce chemotactic responses from HMECs; we evaluated the effect of these chemokines on IL-8-induced chemotaxis of HMECs
  • We have compared the expression of receptors for the CXC chemokine family on human microvascular endothelial cells with human umbilical vein endothelial cells to test the hypothesis that HMECs may be better indicators of the role of chemokines in somatic angiogenesis and to evaluate the prediction that differences in receptor expression are responsible for different functional abilities of various EC types
  • By FACS, confocal microscopy, detection of calcium flux, receptor internalization, and chemotaxis we found that all HMEC and a minority of HUVEC preparations display functional CXC type receptors 1 through 3
  • We have not been able to change the phenotypes of HUVECs to resemble those of HMECs, we cannot rule out the possibility that differences in their functional responsiveness represent a consequence of different endogenous conditions typically encountered by microvascular and large blood vessel ECs
  • We have not been able to change the phenotypes of human umbilical vein endothelial cells to resemble those of human microvascular dermal endothelial cells, we cannot rule out the possibility that differences in their functional responsiveness represent a consequence of different endogenous conditions typically encountered by microvascular and large blood vessel ECs. We are continuing to explore various means of inducing chemokine receptor expression on HUVECs to learn more about the regulation of chemokine receptor expression and are investigating the basis for the inhibitory effects of angiostatic chemokines

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