ENHANCED LEUKOCYTE BINDING BY INTESTINAL MICROVASCULAR ENDOTHELIAL-CELLS IN INFLAMMATORY BOWEL-DISEASE

Background & Aims: Microvascular endothelial cells mediate leukocyte h oming, angiogenesis, and inflammation and healing and show tissue-spec ific adhesion molecules and functions. The activation of human intesti nal mucosal microvascular endothelial cells (HIMECs) was studied in vi tro to uncover possible abnormalities associated with inflammatory bow el disease. Methods: HIMECs were isolated from normal and inflammatory bowel disease mucosa and assessed for phenotypic and morphological fe atures, proliferative response, leukocyte binding capacity, and adhesi on molecule expression. Results: Basal proliferation by HIMECs was les s than that of human umbilical vein endothelial cells (HUVECs) but inc reased proportionally more in response to vascular endothelial growth factor. Proinflammatory stimuli induced an activated, spindle-shaped m orphology in HIMEC monolayers. Compared with HUVECs, unstimulated HIME Cs showed less adhesiveness for U937 and MOLT4 cells and neutrophils, but cytokines and lipopolysaccharide substantially increased the bindi ng capacity of HIMECs. HIMECs derived from inflammatory bowel disease mucosa showed a markedly greater leukocyte-binding capacity than norma l mucosal HIMECs. Patterns of intercellular adhesion molecule 1, vascu lar cell adhesion molecule 1 and E-selectin messenger RNA expression w ere distinct in HIMECs, HUVECs, and mucosal mesenchymal cells. Conclus ions: HIMECs represent differentiated endothelial cells with unique fu nctional properties. Their dramatically enhanced capacity to bind leuk ocytes in inflammatory bowel disease suggests that HIMECs play an impo rtant role in initiating or maintaining inflammation.