PMID- 7545470 OWN - NLM STAT- MEDLINE DCOM- 19951019 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 86 IP - 7 DP - 1995 Oct 1 TI - Production of chemokines, interleukin-8 and monocyte chemoattractant protein-1, during monocyte: endothelial cell interactions. PG - 2767-73 AB - The extravasation of leukocytes from the lumen of the vessel to a site of inflammation requires specific binding events. The interaction of leukocytes with endothelium, via specific receptors, may provide intracellular signals that activate extravasating cells. In the present study, we have investigated the production of chemokines, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) during monocyte: endothelial cell interactions. Both unstimulated and interferon-gamma (IFN-gamma)-prestimulated human umbilical vein endothelial cells (HUVEC) produced low constitutive levels of IL-8 and MCP-1. The addition of enriched monocytes with unstimulated HUVEC resulted in synergistic increases in production of both IL-8 and MCP-1. Monocytes cultured with IFN-gamma-preactivated HUVECs demonstrated little additional increase in IL-8 and MCP-1 production in coculture assays compared with unstimulated HUVEC. Northern blot analysis paralleled the protein data, demonstrating upregulated expression of IL-8 and MCP-1 mRNA in stimulated and unstimulated coculture assays. Culture of enriched monocytes and endothelial cells in transwells demonstrated no increases in IL-8 or MCP-1, indicating the necessity for cellular contact for chemokine production. In previous investigations, we have demonstrated that increased monocyte-derived MIP-1 alpha production was induced by intracellular adhesion molecule-1 (ICAM-1) interactions on activated HUVECs. In contrast, addition of anti-ICAM-1 monoclonal antibodies (MoAbs) did not diminish the production of IL-8 and MCP-1 in the present study. Furthermore, neither antibodies to IL-1 nor tumor necrosis factor (TNF) diminished the production of either IL-8 or MCP-1. However, when soluble matrix proteins were added to the coculture to block cellular interactions, the chemokine protein and mRNA levels were significantly decreased. IL-8 production was decreased by both soluble collagen and fibronectin, whereas MCP-1 was decreased by only soluble collagen, suggesting differential activation pathways. These results indicate that IL-8 and MCP-1 production are increased during monocyte and endothelial cell interactions in part due to matrix protein binding mechanisms. This mechanism may serve a role in cell activation, production of chemokines, as well as extravasation and recruitment of additional leukocytes during inflammatory responses. FAU - Lukacs, N W AU - Lukacs NW AD - Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA. FAU - Strieter, R M AU - Strieter RM FAU - Elner, V AU - Elner V FAU - Evanoff, H L AU - Evanoff HL FAU - Burdick, M D AU - Burdick MD FAU - Kunkel, S L AU - Kunkel SL LA - eng GR - HL02401/HL/NHLBI NIH HHS/United States GR - HL31963/HL/NHLBI NIH HHS/United States GR - HL35276/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antibodies, Monoclonal) RN - 0 (Cell Adhesion Molecules) RN - 0 (Chemokine CCL2) RN - 0 (Chemotactic Factors) RN - 0 (Cytokines) RN - 0 (Fibronectins) RN - 0 (Interleukin-8) RN - 0 (RNA, Messenger) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 82115-62-6 (Interferon-gamma) RN - 9007-34-5 (Collagen) SB - IM MH - Antibodies, Monoclonal/pharmacology MH - Cell Adhesion Molecules/immunology/physiology MH - Cell Communication MH - Cells, Cultured MH - Chemokine CCL2 MH - Chemotactic Factors/*biosynthesis/genetics MH - Collagen/pharmacology MH - Cytokines/*biosynthesis MH - Endothelium, Vascular/*cytology/metabolism MH - Fibronectins/pharmacology MH - Humans MH - Intercellular Adhesion Molecule-1/immunology/physiology MH - Interferon-gamma/pharmacology MH - Interleukin-8/*biosynthesis/genetics MH - Kinetics MH - Monocytes/*cytology/metabolism MH - RNA, Messenger/metabolism MH - Umbilical Veins MH - Vascular Cell Adhesion Molecule-1 EDAT- 1995/10/01 00:00 MHDA- 1995/10/01 00:01 CRDT- 1995/10/01 00:00 PHST- 1995/10/01 00:00 [pubmed] PHST- 1995/10/01 00:01 [medline] PHST- 1995/10/01 00:00 [entrez] AID - S0006-4971(20)68735-3 [pii] PST - ppublish SO - Blood. 1995 Oct 1;86(7):2767-73.