Recruited inflammatory cells mediate endotoxin-induced lung maturation in preterm fetal lambs

Suhas Kallapur, Timothy Moss, Machiko Ikegami, Richard Jasman, John Newnham, Alan Jobe

Research output: Contribution to journalArticleResearchpeer-review

Abstract

RATIONALE: Chorioamnionitis is paradoxically associated with a decreased incidence of respiratory distress syndrome in preterm infants. In preterm lambs, intraamniotic endotoxin and interleukin 1 (IL-1) induce lung inflammation followed by lung maturation. OBJECTIVE: To test if inflammatory cells are required to mediate induced lung maturation. METHODS: Lung inflammation was induced by intraamniotic injection of endotoxin or IL-1. Inflammatory cell recruitment to the lung was inhibited by an anti-CD18 blocking antibody given intramuscularly to the fetus. Preterm lambs were delivered at 124-d gestation (term = 150 d) 2 or 7 d after exposure to endotoxin/IL-1 or endotoxin/IL-1 + anti-CD18 antibody. MEASUREMENTS: Lung inflammation was measured by bronchoalveolar lavage fluid cell count, inflammatory scoring of lung parenchyma, and expression of proinflammatory cytokines and inducible nitric oxide synthase. Lung maturation was quantitated by surfactant protein mRNA expression, saturated phosphatidylcholine pool size, and pressure-volume curves. MAIN RESULTS: Inhibition of CD18 significantly reduced endotoxin-induced but not IL-1-induced fetal lung inflammatory cell recruitment and activation as well as expression of proinflammatory cytokines. Compared with control lungs, both endotoxin and IL-1 induced lung maturation. Anti-CD18 antibody administration inhibited only endotoxin-induced but not IL-1-induced increases in surfactant protein mRNA and surfactant saturated phosphatidylcholine. Exposure to anti-CD18 antibody moderated endotoxin-induced increases in lung volumes but had no effect on IL-1-induced increases in lung volumes. CONCLUSIONS: (1) Endotoxin- but not IL-1-induced inflammatory cell recruitment in the preterm fetal lamb lung is CD18 dependent; (2) recruited inflammatory cells mediate some aspects of fetal lung maturation.
Original languageEnglish
Pages (from-to)1315 - 1321
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume172
Issue number10
DOIs
Publication statusPublished - 2005
Externally publishedYes

Cite this

Kallapur, Suhas ; Moss, Timothy ; Ikegami, Machiko ; Jasman, Richard ; Newnham, John ; Jobe, Alan. / Recruited inflammatory cells mediate endotoxin-induced lung maturation in preterm fetal lambs. In: American Journal of Respiratory and Critical Care Medicine. 2005 ; Vol. 172, No. 10. pp. 1315 - 1321.
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abstract = "RATIONALE: Chorioamnionitis is paradoxically associated with a decreased incidence of respiratory distress syndrome in preterm infants. In preterm lambs, intraamniotic endotoxin and interleukin 1 (IL-1) induce lung inflammation followed by lung maturation. OBJECTIVE: To test if inflammatory cells are required to mediate induced lung maturation. METHODS: Lung inflammation was induced by intraamniotic injection of endotoxin or IL-1. Inflammatory cell recruitment to the lung was inhibited by an anti-CD18 blocking antibody given intramuscularly to the fetus. Preterm lambs were delivered at 124-d gestation (term = 150 d) 2 or 7 d after exposure to endotoxin/IL-1 or endotoxin/IL-1 + anti-CD18 antibody. MEASUREMENTS: Lung inflammation was measured by bronchoalveolar lavage fluid cell count, inflammatory scoring of lung parenchyma, and expression of proinflammatory cytokines and inducible nitric oxide synthase. Lung maturation was quantitated by surfactant protein mRNA expression, saturated phosphatidylcholine pool size, and pressure-volume curves. MAIN RESULTS: Inhibition of CD18 significantly reduced endotoxin-induced but not IL-1-induced fetal lung inflammatory cell recruitment and activation as well as expression of proinflammatory cytokines. Compared with control lungs, both endotoxin and IL-1 induced lung maturation. Anti-CD18 antibody administration inhibited only endotoxin-induced but not IL-1-induced increases in surfactant protein mRNA and surfactant saturated phosphatidylcholine. Exposure to anti-CD18 antibody moderated endotoxin-induced increases in lung volumes but had no effect on IL-1-induced increases in lung volumes. CONCLUSIONS: (1) Endotoxin- but not IL-1-induced inflammatory cell recruitment in the preterm fetal lamb lung is CD18 dependent; (2) recruited inflammatory cells mediate some aspects of fetal lung maturation.",
author = "Suhas Kallapur and Timothy Moss and Machiko Ikegami and Richard Jasman and John Newnham and Alan Jobe",
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Recruited inflammatory cells mediate endotoxin-induced lung maturation in preterm fetal lambs. / Kallapur, Suhas; Moss, Timothy; Ikegami, Machiko; Jasman, Richard; Newnham, John; Jobe, Alan.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 172, No. 10, 2005, p. 1315 - 1321.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Recruited inflammatory cells mediate endotoxin-induced lung maturation in preterm fetal lambs

AU - Kallapur, Suhas

AU - Moss, Timothy

AU - Ikegami, Machiko

AU - Jasman, Richard

AU - Newnham, John

AU - Jobe, Alan

PY - 2005

Y1 - 2005

N2 - RATIONALE: Chorioamnionitis is paradoxically associated with a decreased incidence of respiratory distress syndrome in preterm infants. In preterm lambs, intraamniotic endotoxin and interleukin 1 (IL-1) induce lung inflammation followed by lung maturation. OBJECTIVE: To test if inflammatory cells are required to mediate induced lung maturation. METHODS: Lung inflammation was induced by intraamniotic injection of endotoxin or IL-1. Inflammatory cell recruitment to the lung was inhibited by an anti-CD18 blocking antibody given intramuscularly to the fetus. Preterm lambs were delivered at 124-d gestation (term = 150 d) 2 or 7 d after exposure to endotoxin/IL-1 or endotoxin/IL-1 + anti-CD18 antibody. MEASUREMENTS: Lung inflammation was measured by bronchoalveolar lavage fluid cell count, inflammatory scoring of lung parenchyma, and expression of proinflammatory cytokines and inducible nitric oxide synthase. Lung maturation was quantitated by surfactant protein mRNA expression, saturated phosphatidylcholine pool size, and pressure-volume curves. MAIN RESULTS: Inhibition of CD18 significantly reduced endotoxin-induced but not IL-1-induced fetal lung inflammatory cell recruitment and activation as well as expression of proinflammatory cytokines. Compared with control lungs, both endotoxin and IL-1 induced lung maturation. Anti-CD18 antibody administration inhibited only endotoxin-induced but not IL-1-induced increases in surfactant protein mRNA and surfactant saturated phosphatidylcholine. Exposure to anti-CD18 antibody moderated endotoxin-induced increases in lung volumes but had no effect on IL-1-induced increases in lung volumes. CONCLUSIONS: (1) Endotoxin- but not IL-1-induced inflammatory cell recruitment in the preterm fetal lamb lung is CD18 dependent; (2) recruited inflammatory cells mediate some aspects of fetal lung maturation.

AB - RATIONALE: Chorioamnionitis is paradoxically associated with a decreased incidence of respiratory distress syndrome in preterm infants. In preterm lambs, intraamniotic endotoxin and interleukin 1 (IL-1) induce lung inflammation followed by lung maturation. OBJECTIVE: To test if inflammatory cells are required to mediate induced lung maturation. METHODS: Lung inflammation was induced by intraamniotic injection of endotoxin or IL-1. Inflammatory cell recruitment to the lung was inhibited by an anti-CD18 blocking antibody given intramuscularly to the fetus. Preterm lambs were delivered at 124-d gestation (term = 150 d) 2 or 7 d after exposure to endotoxin/IL-1 or endotoxin/IL-1 + anti-CD18 antibody. MEASUREMENTS: Lung inflammation was measured by bronchoalveolar lavage fluid cell count, inflammatory scoring of lung parenchyma, and expression of proinflammatory cytokines and inducible nitric oxide synthase. Lung maturation was quantitated by surfactant protein mRNA expression, saturated phosphatidylcholine pool size, and pressure-volume curves. MAIN RESULTS: Inhibition of CD18 significantly reduced endotoxin-induced but not IL-1-induced fetal lung inflammatory cell recruitment and activation as well as expression of proinflammatory cytokines. Compared with control lungs, both endotoxin and IL-1 induced lung maturation. Anti-CD18 antibody administration inhibited only endotoxin-induced but not IL-1-induced increases in surfactant protein mRNA and surfactant saturated phosphatidylcholine. Exposure to anti-CD18 antibody moderated endotoxin-induced increases in lung volumes but had no effect on IL-1-induced increases in lung volumes. CONCLUSIONS: (1) Endotoxin- but not IL-1-induced inflammatory cell recruitment in the preterm fetal lamb lung is CD18 dependent; (2) recruited inflammatory cells mediate some aspects of fetal lung maturation.

UR - http://ajrccm.atsjournals.org/cgi/reprint/172/10/1315

U2 - 10.1164/rccm.200506-1007OC

DO - 10.1164/rccm.200506-1007OC

M3 - Article

VL - 172

SP - 1315

EP - 1321

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 10

ER -