Toll-like Receptor and Cytokine Gene Expression in the Early Phase of Human Lung Transplantation

Andrade, Cristiano Feijó; Kaneda, Hidehiro; Der, Sandy D.; Tsang, Melanie; Lodyga, Monika; Santos, Claudia C Dos; Keshavjee, Shaf; Liu, Mingyao

doi:10.1016/j.healun.2006.09.017

Cited by 54 publications

(41 citation statements)

References 35 publications

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“…This report may also help explain why noninfectious local lung injury, such as ischemiareperfusion and gastroesophageal reflux, have been linked to rejection in some studies (16,17). It has been recently reported that innate immune activation occurs in the lung during ischemia reperfusion injury (18). We also know that endogenous toll-receptor ligands such as hyaluronan are increased in lung transplant recipients (19,20).…”

Section: Discussionmentioning

confidence: 75%

Alloimmune Lung Injury Induced by Local Innate Immune Activation Through Inhaled Lipopolysaccharide

et al. 2007

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Background-Alloimmune lung injury, characterized by perivascular lymphocytic inflammation, lymphocytic bronchiolitis (LB), and obliterative bronchiolitis (OB), causes substantial morbidity and mortality after lung transplantation and bone marrow transplantation (BMT), but little is known regarding its pathogenesis. We have developed and pursued the hypothesis that local activation of pulmonary innate immunity through toll-like receptor (TLR)-4 is critical to the development of posttransplant alloimmune lung injury.

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Section: Discussionmentioning

confidence: 75%

Alloimmune Lung Injury Induced by Local Innate Immune Activation Through Inhaled Lipopolysaccharide

et al. 2007

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“…Adult mouse macrophages induce TLR3 expression in response to LPS, whereas human cells do not show a similar increase (30). TLR3 is the only toll-like receptor that does not correlate to reperfusion injury in adult human lung transplant tissues (31).…”

Section: Discussionmentioning

confidence: 90%

Toll-Like Receptors and Agonist Responses in the Developing Fetal Sheep Lung

et al. 2008

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Toll-like receptors (TLRs) are pattern recognition molecules that initiate innate immune responses. Intra-amniotic exposure of fetal sheep to pro-inflammatory stimuli causes pulmonary inflammation and induced lung maturation. We examined TLR ontogeny and fetal lung responsiveness to three different TLR agonists. We cloned ovine TLRs 2, 3, and 4 and found 83-88% homology between these ovine and human TLRs. Lung TLR2 and 4 mRNAs increased throughout late gestation to 50% of adult level in the term newborn lamb. Doses of 10 mg of PAMCysK 4 (TLR2 agonist), poly I:C dsRNA (TLR3 agonist), or E. coli O55:B5 lipopoysaccharide (LPS) (TLR4 agonist) were given by intra-amniotic injection 2 d or 7 d before operative delivery of preterm lambs at 123 d (n ϭ 4 -7/group). The TLR4 agonist induced lung inflammation and maturation, whereas the TLR2 agonist gave less consistent responses. Intra-amniotic LPS increased TLR2 mRNA expression primarily in the inflammatory cells and TLR4 mRNA diffusely in multiple cell types. The TLR3 agonist had no effects, and TLR3 mRNA in the fetal lung did not change after LPS exposure. We conclude that TLR2 and TLR4 mRNAs increase through gestation and expression of TLR2

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“…(11). Our previous work has also indicated that donor innate immune system histories may reflect, in part, the effects of donor management in that mRNA levels of toll-like receptors and specific pathogen recognition molecules are correlated with the donor intubation time (12).…”

Section: Donor-related Factors Clearly Play An Important Role In the mentioning

confidence: 96%

Impact of Human Donor Lung Gene Expression Profiles on Survival after Lung Transplantation: A Case-Control Study

Anraku

Cameron

Waddell

et al. 2008

American Journal of Transplantation

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Primary graft dysfunction (PGD) continues to be a major cause of early death after lung transplantation. Moreover, there remains a lack of accurate pretransplant molecular markers for predicting PGD. To identify distinctive donor lung gene expression signatures associated with PGD, we profiled human donor lungs using microarray technology prior to implantation. The genomic profiles of 10 donor lung samples from patients who subsequently developed clinically defined severe PGD were compared with 16 case-matched donor lung samples from those who had a favorable outcome without PGD (development set, n = 26). Selected PCR validated predictive genes were tested by quantitative reverse transcription-polymerase chain reaction in an independent test set (n = 81). Our microarray analyses of the development set identified four significantly upregulated genes (ATP11B, FGFR2, EGLN1 and MCPH1) in the PGD samples. These genes were also significantly upregulated in donor samples of the test set of patients with poor outcomes when compared to those of patients with good outcomes after lung transplantation. This type of biological donor lung assessment shows significant promise for development of a more accurate diagnostic strategy to assess donor lungs prior to implantation.

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Toll-like Receptor and Cytokine Gene Expression in the Early Phase of Human Lung Transplantation

Cited by 54 publications

References 35 publications

Alloimmune Lung Injury Induced by Local Innate Immune Activation Through Inhaled Lipopolysaccharide

Alloimmune Lung Injury Induced by Local Innate Immune Activation Through Inhaled Lipopolysaccharide

Toll-Like Receptors and Agonist Responses in the Developing Fetal Sheep Lung

Impact of Human Donor Lung Gene Expression Profiles on Survival after Lung Transplantation: A Case-Control Study

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