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This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/L345    most recent 00003.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Kramer, B. W. Articles by Kallapur, S. G. Search for Related Content PubMed PubMed Citation Articles by Kramer, B. W. Articles by Kallapur, S. G.

Endotoxin-induced maturation of monocytes in preterm fetal sheep lung

¹University Hospital Maastricht, Maastricht, The Netherlands; ²Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Ohio; ³School of Women's and Infants' Health, The University of Western Australia, Perth, Australia; and ⁴University 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