Release of CXC-chemokines by human lung microvascular endothelial cells (LMVEC) compared with macrovascular umbilical vein endothelial cells

In the present study, the sensitivity of LMVEC and human umbilical vein end othelial cells (HUVEC) to Lipopolysaccharide (LPS) and the proinflammatory cytokines IL-1, tumour necrosis factor-alpha (TNF-alpha) and interferon-gam ma (IFN-gamma) was compared. To this end, the production of the CC- (MCP-1) , CXC- (IL-8, ENA-78, Gro alpha, NAP-2, GCP-2) and CX3C (fractalkine) chemo kines was studied. A low basal production of these chemokines was observed in both cell types. TNF-alpha, IL-1 and LPS upregulated all chemokines test ed. IFN-gamma however was only able to up-regulate MCP-1 production. LMVEC were more sensitive to IL-1 and LPS compared with HUVEC, since LMVEC produc ed significantly more MCP-1, ENA-78 and Gro alpha (P < 0.01) under these co nditions. Maximal production of MCP-1 in LMVEC was achieved with TNF-alpha (28.4 ng/ml, P < 0.01), whereas IL-1 was the most potent stimulator of ENA- 78 (2.78 ng/ml. P < 0.001) and Gro alpha (29.2 ng/ml, P < 0.001). IL-8 prod uction in LMVEC cells was maximal after LPS stimulation (28.4 ng/ml), but l ower than on HUVEC (P < 0.01). LPS, TNF-alpha and IL-1 stimulation strongly up-regulated all chemokine mRNA. No quantitative differences in mRNA expre ssion between LMVEC and HUVEC were detected for MCP-1 and Gro alpha after L PS stimulation. mRNA expression of ENA-78, GCP-2, CX3C and NAP-2 was howeve r higher in LMVEC under LPS stimulation. In contrast. IL-8 mRNA was slightl y more expressed in HUVEC under these conditions. These results further sup port the hypothesis that the microvascular lung endothelium plays an active role in the induction and perpetuation of acute lung injury.