Stromal activation and formation of lymphoid-like stroma in chronic lung allograft dysfunction.
Transplantation
; 91(12): 1398-405, 2011 Jun 27.
Article
em En
| MEDLINE
| ID: mdl-21512432
ABSTRACT
BACKGROUND:
Lymphoid neogenesis is associated with the development of chronic lung allograft dysfunction (CLAD). Activation of stromal resident cells may be an important mechanism of lymphoid neogenesis.METHODS:
Twenty CLAD lungs explanted for retransplantation were immunohistochemically examined for lymphoid neogenesis, ectopic lymphoid chemokines, and dendritic cells (DCs). Formation of peripheral lymph node addressin (PNAd)+ high endothelial venule (HEV)-like vessels was examined in 134 transbronchial biopsies taken over 2 years posttransplant from 20 consecutive lung transplant recipients.RESULTS:
CLAD lungs were characterized by higher grades of CXCL12 in alveolar (P=0.002) and airway epithelial cells (P=0.001), CCL21+ lymph vessels (P=0.01), and infiltration of DC-specific intercellular adhesion molecule-grabbing nonintegrin+ immature DCs (P=0.056) than normal control lungs. Activation of stromal resident cells in CLAD lungs was highlighted by formation of lymphoid-like stroma including expression of CCL21 and CXCL13, fibroblastic reticular-like cells and DC-specific lysosome-associated membrane protein+ mature DCs in association with a significantly larger number of lymphoid aggregates (P<0.001) with lymphangitc distribution compared with normal lungs. A larger number of PNAd+ HEV-like vessels were also observed outside of lymphoid aggregates with a lymphangitic distribution (P<0.001). HEV-like vessels in transbronchial biopsies were more graded in lungs that eventually developed CLAD (n=7) than those that did not (n=13) by 3 years after transplantation (P=0.001).CONCLUSION:
Lymphoid neogenesis associated with CLAD accompanies activation of stromal resident cells and formation of lymphoid-like stroma. Induction of PNAd+ HEV-like vessels occurs before the manifestation of CLAD.
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Base de dados:
MEDLINE
Assunto principal:
Transplante Homólogo
/
Transplante de Pulmão
/
Tecido Linfoide
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article