Chemokines, chemokine receptors and adhesion molecules on different human endothelia: discriminating the tissue-specific functions that affect leucocyte migration

Abstract

SUMMARYThe selective accumulation of different leucocyte populations during inflammation is regulated by adhesion molecules and chemokines expressed by vascular endothelium. This study examined how chemokine production and the expression of adhesion molecules and chemokine receptors vary between endothelia from different vascular beds. Human saphenous vein endothelium was compared with lung and dermal microvascular endothelia and with umbilical vein endothelium and a bone-marrow endothelial cell line. All endothelia produced CCL2 and CXCL8 constitutively, whereas CXCL10 and CCL5 were only secreted after tumour necrosis factor (TNF)-a or interferon (IFN)-g stimulation. In combination with TNF-a , IFN-g suppressed CXCL8 but enhanced CCL5 and CXCL10, whereas transforming growth factor (TGF)-b reduced secretion of all chemokines. Basal chemokine secretion was higher from umbilical vein than other endothelial cells. Chemokine receptors, CXCR1, CXCR3 and CCR3, were present on all endothelia but highest on saphenous vein. CCR4, CCR5, CCR6, CXCR2, CXCR4 and CXCR5 were also detected at variable levels on different endothelia. The variation between endothelia in chemokine secretion was much greater than the variations in adhesion molecules, both on resting cells and following cytokine stimulation. These results indicate that it is the tissue-specific variations in endothelial chemokine secretion rather than variations in adhesion molecules that can explain the different patterns of inflammation and leucocyte traffic seen in non-lymphoid tissues.

Interferon‐γ protects against the development of structural damage in experimental arthritis by regulating polymorphonuclear neutrophil influx into diseased joints

“…To define the mechanism by which IFN␥ might regulate this process, we used an in vitro model system using the structural cells that constitute the inflammatory pannus, namely, FLS cultured from human RA synovial tissue specimens. In these experiments, we observed that while both IL-1␤ and TNF␣ were potent activators of CXCL8 production, a phenomenon demonstrated previously in many cell types (42)(43)(44)(45)(46)(47), coincubation with IFN␥ (which did not itself induce CXCL8) significantly reduced RA FLS CXCL8 production.…”

Rosiglitazone attenuates the age-related changes in astrocytosis and the deficit in LTP

“…Expression of RANTES in astrocytes and endothelial cells is stimulated by inflammatory cytokines like TNF-␣ (Croitoru-Lamoury et al, 2003;Hillyer et al, 2003). Conversely, RANTES can also increase the expression of TNF-␣ from astrocytes (Luo et al, 2002).…”

Unique and redundant roles of α4 and β2 integrins in kinetics of recruitment of lymphoid vs myeloid cell subsets to the inflamed peritoneum revealed by studies of genetically deficient mice

“…While neutrophil migration to the heart and lung tissues is mediated by both α4 and β2 integrins [34,35], migration of neutrophils to the skin in non-allergic inflammation depends primarily on β2 integrins [17,36]. Tissue-specific variations in chemokine secretion and expression of adhesion molecules in local inflammatory milieu may explain different patterns of integrin usage by leukocytes during their migration to the various tissues [37].…”