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* Laboratory of Molecular Immunoregulation,
Division of Basic Sciences, ABL-BRP, Data Management Services, Inc., Frederick, Maryland 21702, USA; and
NCI, Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA
1Correspondence: NCI-Frederick Cancer Research and Development Center, Bldg. 560, Rm. 21–89A, Frederick, MD 21702-1201, USA. E-mail: oppenhei{at}ncifcrf.gov
The basis for the angiogenic effects of CXC chemokines such as
interleukin 8 (IL-8) and for angiostatic chemokines such as
interferon-inducible protein 10 (IP-10) has been difficult to assess.
We recently reported, based on an RNase protection assay, that human
umbilical vein endothelial cells (HUVECs) did not express detectable
mRNA for the IL-8 receptors CXCR1 and CXCR2. This raised the
possibility of heterogeneity of receptor expression by different
endothelial cell (ECs) types. Since systemic angiogenesis induced by
IL-8 would more likely involve microvessel ECs, we investigated CXC
receptor expression on human microvascular dermal endothelial cells
(HMECs). By confocal microscopy and immunofluorescence we observed that
HMECs consistently expressed high levels of CXCR1 and CXCR4 (mean
fluorescence intensity of 261±22.1 and 306.2±19, respectively) and
intermediate levels of CXCR3 and CXCR2 (173.9±30.2 and 156±30.9,
respectively). In contrast, only a small proportion of HUVEC
preparations expressed low levels of CXCR1, -2, and -3 (66±19.9;
49±15, and 81.4±17.9, respectively). However, both HMECs and HUVECs
expressed equal levels of CXCR4. As expected, HMECs had more potent
chemotactic responses to IL-8 than HUVECs, and this was correlated with
the levels of IL-8 receptors on the ECs. Antibodies to CXCR1 and CXCR2
each had inhibitory effects on chemotaxis of HMECs to IL-8, indicating
that both IL-8 receptors contributed to the migratory response of these
cells toward IL-8. Assessment of the functional capacity of CXCR3
unexpectedly revealed that HMECs migrated in response to relatively
higher concentrations (100–500 ng/ml) of each of the ‘angiostatic’
chemokines IP-10, ITAC, and MIG. Despite this, the ‘angiostatic’
chemokines inhibited the chemotactic response of HMECs to IL-8. IL-8
and SDF-1
but not IP-10 induced calcium mobilization in adherent
ECs, suggesting that signaling events associated with calcium
mobilization are separable from those required for chemotaxis. Taken
together, our data indicated that functional differences among EC types
is dependent on the level of the expression of CXC chemokine receptors.
Whether this heterogeneity in receptor expression by ECs reflects
distinct differentiation pathways remains to be established.—Salcedo,
R., Resau, J. H., Halverson, D., Hudson, E. A., Dambach, M.,
Powell, D., Wasserman, K., Oppenheim, J. J. Differential
expression and responsiveness of chemokine receptors (CXCR1–3) by
human microvascular endothelial cells and umbilical vein endothelial
cells.
Key Words: chemokines • angiogenesis
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|
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