title: Differential regulation of C-C chemokines during fibroblast-monocyte interactions: adhesion vs. inflammatory cytokine pathways.
abstract: The cell-to-cell interactions during chronic inflammatory diseases likely contribute to leukocyte accumulation leading to increased pathology and organ dysfunction. In particular, there is a paucity of information relating to the maintenance of chronic fibrotic diseases. Using a lung fibroblast line and enriched monocyte populations, we have investigated the activational events which contribute to the production of two C-C chemokines, macrophage inflammatory protein-1 alpha (MIP-1alpha) and monocyte chemoattractant protein-1 (MCP-1), during fibroblast-monocyte interactions. Neither the fibroblast cell line (16lu) nor isolated monocytes alone produced significant levels of MIP-1alpha or MCP-1. However, when isolated monocytes were layered onto 16 lu fibroblast monolayers a significant increase in MIP-1alpha and MCP-1 production was observed. The use of fixed cell populations indicated that the MIP-1alpha was derived from monocytes and MCP-1 from both cell populations. To examine the molecules which were required for chemokine production during the interaction, specific antibodies were used in the co-cultures. Blocking beta3-integrin interactions significantly inhibited MIP-1alpha production. In contrast, beta-integrin interactions had no effect on the MCP-1 production, while, neutralization of TNF significantly decreased MCP-1 production during the co-culture. These data indicate that fibroblast-monocyte interactions induce chemokine production through different mechanisms and a combination of these responses may contribute to the maintenance of the mononuclear cell accumulation during disease progression.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zickus
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: K
authors.initials: K
authors.lastname: Simpson
authors.forename: H
authors.initials: H
authors.lastname: Evanoff
authors.forename: M
authors.initials: M
authors.lastname: Glass
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
authors.forename: N W
authors.initials: NW
authors.lastname: Lukacs
mesh_terms: D002448:Cell Adhesion; D002450:Cell Communication; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000096:biosynthesis*; D016207:Cytokines / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D019012:Integrin beta1 / Q000502:physiology; D009000:Monocytes / Q000502:physiology*
chemical_list: D019742:Chemokines, CC; D016207:Cytokines; D019012:Integrin beta1