The extravasation of leukocytes from the lumen of the vessel to a site of inflammation initially requires a specific binding event followed by migration of the cells through the endothelial cell layer into the inflammatory foci. The interaction of leukocytes with the endothelium via specific receptors may provide intracellular signals that activate the cells. In the present study we have investigated the production of MIP-1 alpha, a mononuclear cell chemotactic protein, during monocyte:endothelial cell interactions. Neither unstimulated nor interferon (IFN)-stimulated human umbilical vein endothelial cells (HUVECs) produced substantial MIP-1 alpha protein. However, the addition of enriched monocyte populations with unstimulated HUVECs resulted in the production of MIP-1 alpha. Monocytes cultured with IFN- gamma-activated HUVECs showed an additional increase in MIP-1 alpha production. Immunohistochemical analysis demonstrated that the monocyte was the cellular source of MIP-1 alpha production in this coculture system. The mechanism of MIP-1 alpha expression was further assessed by determining the role of adhesion molecules in the regulation of MIP-1 alpha production during monocyte:HUVEC interactions. To attenuate the increased production of MIP-1 alpha by the monocyte:HUVEC interaction, anti-adhesion molecule monoclonal antibodies (MoAbs) were added to the cultures. Addition of anti-ICAM-1 neutralizing MoAbs significantly inhibited the production of MIP-1 alpha, whereas neutralizing anti-VCAM- 1 MoAbs failed to block MIP-1 alpha production. Furthermore, MIP-1 alpha production was induced in monocytes cultured on ICAM-1-coated plates. These results indicate an intimate relationship between leukocyte-endothelial cells, adhesion molecule, and the expression of the monocyte-derived chemokine MIP-1 alpha during cellular adhesion. This mechanism may serve an important role in cell activation and recruitment of leukocytes during the initiation of an inflammatory response.
Intercellular adhesion molecule-1 mediates the expression of monocyte- derived MIP-1 alpha during monocyte-endothelial cell interactions
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NW Lukacs, RM Strieter, VM Elner, HL Evanoff, M Burdick, SL Kunkel; Intercellular adhesion molecule-1 mediates the expression of monocyte- derived MIP-1 alpha during monocyte-endothelial cell interactions. Blood 1994; 83 (5): 1174–1178. doi: https://doi.org/10.1182/blood.V83.5.1174.bloodjournal8351174
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