CXC and CC chemokine receptors on coronary and brain endothelia

Background: Chemokine receptors on leukocytes play a key role in inflammati on and HIV-1 infection. Chemokine receptors on endothelia may serve an impo rtant 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 ce lls (CAEC) in vitro and cryostat sections of the heart tissue was determine d by light and confocal microscopy and now cytometry with monodonal antibod ies. Chemotaxis of endothelia by CC chemokines was evaluated in a transmigr ation assay. Results: In BMVEC, the chemokine receptors CCR3 and CXCR4 showed the strong est expression. CXCR4 was localized by confocal microscopy to both the cyto plasm and the plasma membrane of BMVEC. In CAEC, CXCR4 demonstrated a stron g expression with predominantly periplasmic localization. CCR5 expression w as detected both in BMVEC and CAEC but at a lower level. Human strongly CXC R4 but only weakly CCR3 and CCRS5. Two additional CC chemokines, CCR2A and CCR4, were detected in BMVEC and CAEC by immunostaining. Immunocytochemistr y of the heart tissues with monoclonal antibodies revealed a high expressio n of CXCR4 and CCR2A and a low expression of CCR3 and CCR5 on coronary vess el endothelia. Coronary endothelia showed in vitro a strong chemotactic res ponse to the CC chemokines RANTEs, MIP-1 alpha, and MIP-1 beta. Conclusions: The endothelia isolated from the brain display strongly both t he CCR3 and CXCR4 HIV-1 coreceptors, whereas the coronary endothelia expres s strongly only the CXCR4 coreceptor. CCR5 is expressed at a lower level in both endothelia. The differential display of CCR3 on the brain and coronar y endothelia could be significant with respect to the differential suscepti bility 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 rec eptors could play a role in endothelial migration and repair.