Endotoxin-induced maturation of monocytes in preterm fetal sheep lung

• Published in: American journal of physiology. Lung cellular and molecular physiology 2007-08, Vol.293 (2), p.L345-L353
• Main Authors: Kramer, Boris W, Joshi, Shubhada N, Moss, Timothy J. M, Newnham, John P, Sindelar, Richard, Jobe, Alan H, Kallapur, Suhas G
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Apoptosis - immunology; Cells; Chorioamnionitis - chemically induced; Chorioamnionitis - immunology; Endotoxins - immunology; Endotoxins - pharmacology; Escherichia coli; Female; Fetuses; Gestational Age; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Immunophenotyping; Interleukin-6 - metabolism; Lung - embryology; Lung - immunology; Lungs; Macrophages - cytology; Macrophages - drug effects; Macrophages - immunology; Monocytes - cytology; Monocytes - drug effects; Monocytes - immunology; Neutrophils - cytology; Neutrophils - immunology; Phagocytosis - immunology; Pregnancy; Proto-Oncogene Proteins - metabolism; Recombinant Proteins - pharmacology; Respiratory diseases; RNA, Messenger - metabolism; Sheep; Trans-Activators - metabolism; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00003.2007

1 University Hospital Maastricht, Maastricht, The Netherlands; 2 Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Ohio; 3 School of Women's and Infants' Health, The University of Western Australia, Perth, Australia; and 4 University Children's Hospital Würzburg, Würzburg, Germany Submitted 4 January 2007 ; accepted in final form 6 May 2007 The fetal lung normally contains immature monocytes and very few mature macrophages. The chorioamnionitis frequently associated with preterm birth induces monocyte influx into the fetal lung. Previous studies demonstrated that monocytes in the developing lung can mediate lung injury responses that resemble BPD in humans. We hypothesized that chorioamnionitis would induce maturation of immature monocytes in the fetal lung. Groups of three to seven time-mated ewes received saline or 10 mg of endotoxin ( Escherichia coli 055:B5) in saline by intra-amniotic injection for intervals from 1 to 14 days before operative delivery at 124 days of gestational age. Monocytic cells from lung tissue were recovered using Percoll gradients. Monocytic cells consistent with macrophages were identified morphologically and by myosin heavy chain class II expression. An increase in macrophages was preceded by induction of granulocyte-macrophage colony-stimulating factor in the lung and subsequent activation of the transcription factor PU.1. The production of IL-6 by monocytes/macrophages in response to endotoxin challenge in vitro increased 7 and 14 days after exposure to intra-amniotic endotoxin. Recombinant TNF- induced IL-6 production by lung monocytic cells exposed to intra-amniotic endotoxin but not in control cells. Monocytic phagocytosis of apoptotic neutrophils also increased 7 and 14 days after exposure to intra-amniotic endotoxin. Intra-amniotic endotoxin induced lung monocytes to develop into functionally mature cells consistent with macrophages. These findings have implications for lung immune responses after exposure to chorioamnionitis. macrophage; fetal immunity; bronchopulmonary dysplasia; chorioamnionitis; granulocyte-macrophage colony-stimulating factor; PU.1 Address for reprint requests and other correspondence: B. W. Kramer, Dept. of Pediatrics, Academisch ziekenhuis Maastricht, Postbus 5800, 6202 AZ Maastricht, The Netherlands (e-mail: bkra{at}paed.azm.nl )