Alveolar macrophage-derived cytokines induce monocyte chemoattractant protein-1 expression from human pulmonary type II-like epithelial cells

• Published in: The Journal of biological chemistry Vol. 266; no. 15; pp. 9912 - 9918
• Main Authors: STANDIFORD, T. J, KUNKEL, S. L, PHAN, S. H, ROLLINS, B. J, STRIETER, R. M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 25-05-1991
• Subjects: Biological and medical sciences; Blotting, Northern; Cell physiology; Chemokine CCL2; Chemotactic Factors - genetics; Chemotactic Factors - metabolism; Chromatography, High Pressure Liquid; Cytokines - metabolism; Epithelial Cells; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Humans; Interleukin-1 - metabolism; Lung - cytology; Lung - metabolism; Macrophages - metabolism; Molecular and cellular biology; Pulmonary Alveoli - metabolism; Responses to growth factors, tumor promotors, other factors; RNA, Messenger - analysis; Tumor Necrosis Factor-alpha - metabolism; Human; Alveolar type II cell; Induction; Interleukin; Lung; Cytokine; Inflammation; Gene expression; Chemotaxis; Tumor necrosis factor; Protein synthesis; Epithelial cell; Macrophage
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)92905-4

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.