Endotoxin-induced maturation of monocytes in preterm fetal sheep lung

Kramer, Boris W.; Joshi, Shubhada N.; Moss, Timothy; Newnham, John P.; Sindelar, Richard; Jobe, Alan H.; Kallapur, Suhas G.

doi:10.1152/ajplung.00003.2007

Cited by 78 publications

(90 citation statements)

References 48 publications

(67 reference statements)

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“…However, 7 days after a single intra-amniotic LPS exposure, both the lung and the blood monocytes significantly increase IL6 secretion and H 2 O 2 production in response to an in vitro LPS challenge. We also recently reported that lung monocytes precociously mature to macrophages after exposure to intra-amniotic LPS (26). Thus, exposure to intra-amniotic LPS can induce maturation of monocyte function.…”

Section: Discussionmentioning

confidence: 66%

“…Cells from the suspension were then layered over discontinuous Percoll gradients (1.085 and 1.046 g/ml; Amersham Pharmacia Biotech) to separate the lung monocytic cells from the other cells. Monocytic cells were recovered from the interface between the Percoll densities (26). To obtain blood monocytes, cord blood was diluted with PBS (1/1) and layered onto a Percoll gradient as described (16).…”

Section: Lung and Blood Monocyte Isolation And Culturementioning

confidence: 99%

“…Cell surface TLR4 expression was determined by flow cytometry using a sheep cross-reactive anti-TLR4 Ab (BD Biosciences) and an appropriate fluorescence tagged secondary Ab (26). The abundance of IRAK proteins in the monocytes was determined using immunoblots.…”

Section: Tlr4 Il-1r-associated Kinase (Irak)-4 and Irak-m Protein Amentioning

confidence: 99%

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Pulmonary and Systemic Endotoxin Tolerance in Preterm Fetal Sheep Exposed to Chorioamnionitis

Kallapur

Jobe

Ball

et al. 2007

The Journal of Immunology

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109

139

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In a model of human chorioamnionitis, fetal sheep exposed to a single injection, but not repeated injections, of intra-amniotic endotoxin develop lung injury responses. We hypothesized that repeated exposure to intra-amniotic endotoxin induces endotoxin tolerance. Fetal sheep were given intra-amniotic injections of saline (control) or Escherichia coli LPS O55:B5 (10 mg) either 2 days (2-day group, single exposure), 7 days (7-day group, single exposure), or 2 plus 7 days (2- and 7-day repeat exposure) before preterm delivery at 124 days gestation (term = 150 days). Endotoxin responses were assessed in vivo in the lung and liver, and in vitro in monocytes from the blood and the lung. Compared with the single 2-day LPS exposure group, the (2 plus 7 days) repeat LPS-exposed lambs had: 1) decreased lung neutrophil and monocyte inducible NO synthase (NOSII) expression, and 2) decreased lung cytokine and liver serum amyloid A3 mRNA expression. In the lung, serum amyloid A3 mRNA expression decreased in the airway epithelial cells but not in the lung inflammatory cells. Unlike the single 7-day LPS exposure group, peripheral blood and lung monocytes from the repeat-LPS group did not increase IL-6 secretion or hydrogen peroxide production in response to in vitro LPS. Compared with controls, TLR4 expression did not change but IL-1R-associated kinase M expression increased in the monocytes from repeat LPS-exposed lambs. These results are consistent with the novel finding of endotoxin tolerance in preterm fetal lungs exposed to intra-amniotic LPS. The findings have implications for preterm infants exposed to chorioamnionitis for both responses to lung injury and postnatal nosocomial infections.

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Section: Discussionmentioning

confidence: 66%

Section: Lung and Blood Monocyte Isolation And Culturementioning

confidence: 99%

See 1 more Smart Citation

Pulmonary and Systemic Endotoxin Tolerance in Preterm Fetal Sheep Exposed to Chorioamnionitis

Kallapur

Jobe

Ball

et al. 2007

The Journal of Immunology

Self Cite

109

139

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show abstract

“…Interestingly, a macrophage response was involved in the pulmonary inflammatory response to LPS in the course of gestation, shown by an increased PU.1 expression. Normally, the fetal lung contains few macrophages, and monocytes mature to macrophages with PU.1 expression after term birth (14,22,23). The lungs of fetal sheep exposed to intra-amniotic LPS expressed PU.1 within 1-2 d, and vacuolated alveolar macrophages could be recovered by lavage several days later (14).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, intra-amniotic LPS exposure induces (i) maturation of monocytes to alveolar macrophages with increased inflammatory response potentials by inducing hematopoietic transcription factor PU.1 (14) and (ii) cross-tolerance to different Toll-like receptor (TLR) agonists (15). Thus, the naive fetal immune system is capable of complex modulations that can alter subsequent immune function (13).…”

mentioning

confidence: 99%

Effects of intra-amniotic lipopolysaccharide exposure on the fetal lamb lung as gestation advances

et al. 2014

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Background: Intra-amniotic lipopolysaccharide (LPS) exposure may affect neonatal outcome by altering fetal lung and immune system development. We hypothesized that intra-amniotic LPS exposure would cause persistent fetal pulmonary responses as the lungs develop in utero. Methods: Fetal lambs were exposed to intra-amniotic LPS at 118 or at 118 and 123 d of gestational age (GA) with delivery at 125, 133, or 140 d (term = 147 d). Immune responses, PU.1 expression, toll-like receptor (tLR)-1,2,4,6 mRNA levels, mast cell levels, and pulmonary elastin deposition were evaluated. results: After a single dose of LPS, pulmonary inflammatory responses were observed with increases of (i) PU.1 and tLR1 at 125 d GA and (ii) monocytes, lymphocytes, tLR2, and tLR6 at 133 d GA. Repetitive LPS exposure resulted in (i) increases of neutrophils, monocytes, PU.1, and tLR1 at 125 d GA; (ii) increases of neutrophils, PU.1, and tLR2 at 133 d GA; and (iii) decreases of mast cells, elastin foci, tLR4, and tLR6 at early gestation. At 140 d GA, only PU.1 was increased after repetitive LPS exposure. conclusion: The preterm fetal lung can respond to a single exposure or repeated exposures from intra-amniotic LPS in multiple ways, but the absence of inflammatory and structural changes in LPS-exposed fetuses delivered near term suggest that the fetus can resolve an inflammatory stimulus in utero with time.

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Fetal and Maternal Responses to Intraamniotic Infection

Romero¹,

Chaemsaithong²,

Yeo³

et al. 2017

Fetal and Neonatal Physiology

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Endotoxin-induced maturation of monocytes in preterm fetal sheep lung

Abstract: Kramer BW, Joshi SN, Moss TJ, Newnham JP, Sindelar R, Jobe AH, Kallapur SG. Endotoxin-induced maturation of monocytes in preterm fetal sheep lung.

Cited by 78 publications

References 48 publications

Pulmonary and Systemic Endotoxin Tolerance in Preterm Fetal Sheep Exposed to Chorioamnionitis

Pulmonary and Systemic Endotoxin Tolerance in Preterm Fetal Sheep Exposed to Chorioamnionitis

Effects of intra-amniotic lipopolysaccharide exposure on the fetal lamb lung as gestation advances

Fetal and Maternal Responses to Intraamniotic Infection

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