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Ingraft chimerism in lung transplantation--a study in a porcine model of obliterative bronchiolitis.

Päiväniemi OE, Musilova P, Raivio PM, Maasilta PK, Alho HS, Rubes J, Aittomäki K, Salminen US - Respir. Res. (2011)

Bottom Line: Antirejection medication did not prevent, but delayed the appearance of Y chromosome positive cells in the epithelium (p<0.05), or bronchial wall (p<0.05).Chimerism occurred in all allografts, including those without features of OB.Therefore we suggest that ingraft chimerism may be a mechanism involved in the repair of alloimmune-mediated tissue injury after transplantation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cardiothoracic Surgery, Helsinki University Hospital, University of Helsinki, P.O. Box 340, 00029 HUS, Helsinki, Finland. outi.paivaniemi@fimnet.fi

ABSTRACT

Background: Bronchial epithelium is a target of the alloimmune response in lung transplantation, and intact epithelium may protect allografts from rejection and obliterative bronchiolitis (OB). Herein we study the influence of chimerism on bronchial epithelium and OB development in pigs.

Methods: A total of 54 immunosuppressed and unimmunosuppressed bronchial allografts were serially obtained 2-90 days after transplantation. Histology (H&E) was assessed and the fluorescence in situ hybridization (FISH) method for Y chromosomes using pig-specific DNA-label was used to detect recipient derived cells in graft epithelium and bronchial wall, and donor cell migration to recipient organs. Ingraft chimerism was studied by using male recipients with female donors, whereas donor cell migration to recipient organs was studied using female recipients with male donors.

Results: Early appearance of recipient-derived cells in the airway epithelium appeared predictive of epithelial destruction (R=0.610-0.671 and p<0.05) and of obliteration of the bronchial lumen (R=0.698 and p<0.01). All allografts with preserved epithelium showed epithelial chimerism throughout the follow-up. Antirejection medication did not prevent, but delayed the appearance of Y chromosome positive cells in the epithelium (p<0.05), or bronchial wall (p<0.05).

Conclusions: In this study we demonstrate that early appearance of Y chromosomes in the airway epithelium predicts features characteristic of OB. Chimerism occurred in all allografts, including those without features of OB. Therefore we suggest that ingraft chimerism may be a mechanism involved in the repair of alloimmune-mediated tissue injury after transplantation.

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Destruction of airway epithelium (A) and obliteration of the bronchial lumen (B), and the positive staining for Y chromosomes in the epithelium (C) and in the bronchial wall (D). The study groups were non-immunosuppressed, inadequately immunosuppressed, or adequately immunosuppressed. Epithelial destruction, luminal obliteration, and positive staining for Y chromosomes were graded on a scale from 0-3. The number of assessed bronchi in each group and on each assessment point was 6.6. ± 1.1 for histological samples and 7.1. ± 1.1 for FISH.
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Figure 1: Destruction of airway epithelium (A) and obliteration of the bronchial lumen (B), and the positive staining for Y chromosomes in the epithelium (C) and in the bronchial wall (D). The study groups were non-immunosuppressed, inadequately immunosuppressed, or adequately immunosuppressed. Epithelial destruction, luminal obliteration, and positive staining for Y chromosomes were graded on a scale from 0-3. The number of assessed bronchi in each group and on each assessment point was 6.6. ± 1.1 for histological samples and 7.1. ± 1.1 for FISH.

Mentions: After initial ischemic injury, the respiratory epithelium of allografts with no immunosuppression first showed a tendency to restore. Epithelial loss was subtotal on day 7, and was followed by gradual obliteration of the bronchial lumen (Figures 1A and 1B). In the beginning of the follow-up, the inadequately treated allografts showed less extensive epithelial destruction (Figure 2A), the difference in epithelial loss between the inadequately treated group and non-treated group was significant on follow-up days 4, 7, and 10 (p < 0.05). However, by day 30 the lumens of the inadequately treated allografts also occluded totally (Figures 1A and 1B). In the adequately treated group (Figure 2B) and in a control autograft (Figure 2C), only mild epithelial destruction occurred. The difference in epithelial loss between the adequately treated allografts and non-treated allografts was significant from day 7 on (p < 0.05). The difference in epithelial loss between the adequately treated allografts and the inadequately treated allografts was significant from day 10 on (p < 0.05). No obliterative lesions of the bronchial lumens were observed in adequately treated allografts (Figure 1B). Luminal obliteration of adequately treated allografts differed significantly from non-treated allografts on days 10 and 30 (p < 0.05), and from inadequately treated allografts on days 14 and 30 (p < 0.05).


Ingraft chimerism in lung transplantation--a study in a porcine model of obliterative bronchiolitis.

Päiväniemi OE, Musilova P, Raivio PM, Maasilta PK, Alho HS, Rubes J, Aittomäki K, Salminen US - Respir. Res. (2011)

Destruction of airway epithelium (A) and obliteration of the bronchial lumen (B), and the positive staining for Y chromosomes in the epithelium (C) and in the bronchial wall (D). The study groups were non-immunosuppressed, inadequately immunosuppressed, or adequately immunosuppressed. Epithelial destruction, luminal obliteration, and positive staining for Y chromosomes were graded on a scale from 0-3. The number of assessed bronchi in each group and on each assessment point was 6.6. ± 1.1 for histological samples and 7.1. ± 1.1 for FISH.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3111361&req=5

Figure 1: Destruction of airway epithelium (A) and obliteration of the bronchial lumen (B), and the positive staining for Y chromosomes in the epithelium (C) and in the bronchial wall (D). The study groups were non-immunosuppressed, inadequately immunosuppressed, or adequately immunosuppressed. Epithelial destruction, luminal obliteration, and positive staining for Y chromosomes were graded on a scale from 0-3. The number of assessed bronchi in each group and on each assessment point was 6.6. ± 1.1 for histological samples and 7.1. ± 1.1 for FISH.
Mentions: After initial ischemic injury, the respiratory epithelium of allografts with no immunosuppression first showed a tendency to restore. Epithelial loss was subtotal on day 7, and was followed by gradual obliteration of the bronchial lumen (Figures 1A and 1B). In the beginning of the follow-up, the inadequately treated allografts showed less extensive epithelial destruction (Figure 2A), the difference in epithelial loss between the inadequately treated group and non-treated group was significant on follow-up days 4, 7, and 10 (p < 0.05). However, by day 30 the lumens of the inadequately treated allografts also occluded totally (Figures 1A and 1B). In the adequately treated group (Figure 2B) and in a control autograft (Figure 2C), only mild epithelial destruction occurred. The difference in epithelial loss between the adequately treated allografts and non-treated allografts was significant from day 7 on (p < 0.05). The difference in epithelial loss between the adequately treated allografts and the inadequately treated allografts was significant from day 10 on (p < 0.05). No obliterative lesions of the bronchial lumens were observed in adequately treated allografts (Figure 1B). Luminal obliteration of adequately treated allografts differed significantly from non-treated allografts on days 10 and 30 (p < 0.05), and from inadequately treated allografts on days 14 and 30 (p < 0.05).

Bottom Line: Antirejection medication did not prevent, but delayed the appearance of Y chromosome positive cells in the epithelium (p<0.05), or bronchial wall (p<0.05).Chimerism occurred in all allografts, including those without features of OB.Therefore we suggest that ingraft chimerism may be a mechanism involved in the repair of alloimmune-mediated tissue injury after transplantation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cardiothoracic Surgery, Helsinki University Hospital, University of Helsinki, P.O. Box 340, 00029 HUS, Helsinki, Finland. outi.paivaniemi@fimnet.fi

ABSTRACT

Background: Bronchial epithelium is a target of the alloimmune response in lung transplantation, and intact epithelium may protect allografts from rejection and obliterative bronchiolitis (OB). Herein we study the influence of chimerism on bronchial epithelium and OB development in pigs.

Methods: A total of 54 immunosuppressed and unimmunosuppressed bronchial allografts were serially obtained 2-90 days after transplantation. Histology (H&E) was assessed and the fluorescence in situ hybridization (FISH) method for Y chromosomes using pig-specific DNA-label was used to detect recipient derived cells in graft epithelium and bronchial wall, and donor cell migration to recipient organs. Ingraft chimerism was studied by using male recipients with female donors, whereas donor cell migration to recipient organs was studied using female recipients with male donors.

Results: Early appearance of recipient-derived cells in the airway epithelium appeared predictive of epithelial destruction (R=0.610-0.671 and p<0.05) and of obliteration of the bronchial lumen (R=0.698 and p<0.01). All allografts with preserved epithelium showed epithelial chimerism throughout the follow-up. Antirejection medication did not prevent, but delayed the appearance of Y chromosome positive cells in the epithelium (p<0.05), or bronchial wall (p<0.05).

Conclusions: In this study we demonstrate that early appearance of Y chromosomes in the airway epithelium predicts features characteristic of OB. Chimerism occurred in all allografts, including those without features of OB. Therefore we suggest that ingraft chimerism may be a mechanism involved in the repair of alloimmune-mediated tissue injury after transplantation.

Show MeSH
Related in: MedlinePlus