Adhesion molecules (E-selectin and ICAM-1) in pulmonary allograft rejection.
Vascular endothelial cells act as antigen-presenting cells in the lung allograft and stimulate alloreactive host lymphocytes. Activated lymphocytes and cytokines can induce expression of leukocyte-endothelial adhesion molecules that facilitate invasion of the allograft by circulating leukocytes. To define the role of endothelial HLA class II antigen and adhesion molecule expression in lung allograft rejection, we prospectively analyzed endothelial expression of HLA class II, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) antigens in 52 transbronchial biopsy specimens from 24 lung allograft recipients as compared to normal control subjects. Thirty-one of 52 specimens showed histologic rejection and 8 of 24 patients developed histologic obliterative bronchiolitis (OB) by the end of the study period. Increased expression of HLA class II antigen was seen in 32 of 52 (62%) lung allograft specimens, but increased expression did not correlate with acute rejection or OB. In contrast, E-selectin expression was seen in 30 of 52 (58%) biopsy specimens and was associated with acute rejection (p < 0.005) and with the development of OB (p < 0.05). Increased expression of ICAM-1 was seen in only 18 of 52 (35%) biopsy specimens and did not correlate with acute rejection or OB. These data suggest that E-selectin expression may be a tissue marker of acute and chronic lung rejection possibly by promoting leukocyte adhesion to the allograft endothelium. The high levels of endothelial HLA class II expression may reflect long-term antigenic stimulation of the allograft even in the absence of rejection.
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, USA.
R
R
Shreeniwas
L L
LL
Schulman
M
M
Narasimhan
C C
CC
McGregor
C C
CC
Marboe
D000208:Acute Disease; D000276:Adjuvants, Immunologic; D017951:Antigen Presentation; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D001989:Bronchiolitis Obliterans / Q000276:immunology / Q000473:pathology; D002448:Cell Adhesion; D002908:Chronic Disease; D019040:E-Selectin / Q000032:analysis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000276:immunology; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006681:HLA-D Antigens / Q000032:analysis / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis* / Q000235:genetics; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D011446:Prospective Studies; D014184:Transplantation, Homologous
D000276:Adjuvants, Immunologic; D015415:Biomarkers; D019040:E-Selectin; D006681:HLA-D Antigens; D018799:Intercellular Adhesion Molecule-1