title: Alveolar macrophage-derived cytokines induce monocyte chemoattractant protein-1 expression from human pulmonary type II-like epithelial cells.
abstract: Many acute and chronic lung diseases are characterized by the presence of increased numbers of activated macrophages. These macrophages are derived predominantly from newly recruited peripheral blood monocytes and may play a role in the amplification and perpetuation of an initial lung insult. The process of inflammatory cell recruitment is poorly understood, although the expression of inflammatory cell-specific chemoattractants and subsequent generation of chemotactic gradients is likely involved. Although immune cells such as macrophages and lymphocytes are known to generate several inflammatory cell chemoattractants, parenchymal cells can also synthesize and secrete a number of bioactive factors. We now demonstrate the generation of significant monocyte chemotactic activity from tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta-treated pulmonary type II-like epithelial cells (A549). The predominant inducible monocyte chemotaxin had an estimated molecular mass of approximately 14-15 kDa and was neutralized by specific antibody to human monocyte chemotactic protein-1 (MCP-1). Induction of activity was accompanied by increases in steady-state mRNA level for MCP-1. These data are consistent with the induction of MCP-1 expression from A549 cells by TNF and IL-1. MCP-1 production from A549 cells could be induced by lipopolysaccharide (LPS)-stimulated alveolar macrophage (AM)-conditioned media, but not by LPS alone. The inducing activity in AM-conditioned media was neutralized with specific antibodies to IL-1 beta, but not TNF-alpha. Our findings suggest that the alveolar epithelium can participate in inflammatory cell recruitment via the production of MCP-1 and that cytokine networking between contiguous alveolar macrophages and the pulmonary epithelium may be essential for parenchymal cell MCP-1 expression.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0360.
authors.forename: T J
authors.initials: TJ
authors.lastname: Standiford
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: S H
authors.initials: SH
authors.lastname: Phan
authors.forename: B J
authors.initials: BJ
authors.lastname: Rollins
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
mesh_terms: D015152:Blotting, Northern; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha