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CXC and CC chemokine receptors on coronary and brain endothelia
1Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095-1769, USA.
Insights
Endothelial cells in the brain express CCR3 and CXCR4, while heart vessels express CXCR4. This differential chemokine receptor expression may influence HIV-1 invasion and endothelial repair.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Chemokine receptors on leukocytes are crucial for inflammation and HIV-1 infection.
- Endothelial chemokine receptors may impact HIV-1 tissue invasion and angiogenesis.
Purpose of the Study:
- To investigate the expression of chemokine receptors on brain and coronary artery endothelial cells.
- To determine the role of these receptors in endothelial function and HIV-1 susceptibility.
Main Methods:
- Utilized light and confocal microscopy, flow cytometry, and monoclonal antibodies to assess chemokine receptor expression in human brain microvascular endothelial cells (BMVEC) and coronary artery endothelial cells (CAEC).
- Evaluated endothelial cell chemotaxis using a transmigration assay.
- Examined chemokine receptor expression in cryostat sections of heart tissue.
Main Results:
- BMVEC strongly expressed CCR3 and CXCR4; CAEC strongly expressed CXCR4. CCR5 was detected at lower levels in both.
- Heart tissue endothelium showed high expression of CXCR4 and CCR2A, and low expression of CCR3 and CCR5.
- Coronary endothelia demonstrated a significant chemotactic response to RANTES, MIP-1alpha, and MIP-1beta.
Conclusions:
- Differential expression of CCR3 on brain versus coronary endothelia may affect HIV-1 invasion susceptibility.
- CXCR4 is a key coreceptor on both brain and coronary endothelia.
- Chemokine receptors like CCR2A, CCR3, CCR5, and CXCR4 may play roles in endothelial migration and tissue repair.
Background:
Chemokine receptors on leukocytes play a key role in inflammation and HIV-1 infection. Chemokine receptors on endothelia may serve an important role in HIV-1 tissue invasion and angiogenesis.
Materials And Methods:
The expression of chemokine receptors in human brain microvascular endothelial cells (BMVEC) and coronary artery endothelial cells (CAEC) in vitro and cryostat sections of the heart tissue was determined by light and confocal microscopy and flow cytometry with monoclonal antibodies. Chemotaxis of endothelia by CC chemokines was evaluated in a transmigration assay.
Results:
In BMVEC, the chemokine receptors CCR3 and CXCR4 showed the strongest expression. CXCR4 was localized by confocal microscopy to both the cytoplasm and the plasma membrane of BMVEC. In CAEC, CXCR4 demonstrated a strong expression with predominantly periplasmic localization. CCR5 expression was detected both in BMVEC and CAEC but at a lower level. Human umbilical cord endothelial cells (HUVEC) expressed strongly CXCR4 but only weakly CCR3 and CCR5. Two additional CC chemokines, CCR2A and CCR4, were detected in BMVEC and CAEC by immunostaining. Immunocytochemistry of the heart tissues with monoclonal antibodies revealed a high expression of CXCR4 and CCR2A and a low expression of CCR3 and CCR5 on coronary vessel endothelia. Coronary endothelia showed in vitro a strong chemotactic response to the CC chemokines RANTES, MIP-1alpha, and MIP-1beta.
Conclusions:
The endothelia isolated from the brain display strongly both the CCR3 and CXCR4 HIV-1 coreceptors, whereas the coronary endothelia express strongly only the CXCR4 coreceptor. CCR5 is expressed at a lower level in both endothelia. The differential display of CCR3 on the brain and coronary endothelia could be significant with respect to the differential susceptibility of the heart and the brain to HIV-1 invasion. In addition, CCR2A is strongly expressed in the heart endothelium. All of the above chemokine receptors could play a role in endothelial migration and repair.