Allogeneic bronchoalveolar lavage cells induce the histology and immunology of lung allograft rejection in recipient murine lungs: role of intercellular adhesion molecule-1 on donor cells.
BACKGROUND
Intercellular adhesion molecule (ICAM)-1 expressed on accessory cells has a key role in antigen presentation. The histology and immunology of lung allograft rejection is postulated to result from donor lung accessory cells presenting alloantigens to recipient lymphocytes, and, therefore, ICAM-1 may have a crucial role in the rejection process. We have previously reported that the instillation of allogeneic (C57BL/6, I-a(b)) bronchoalveolar lavage (BAL) cells (96% macrophages, 2% dendritic cells) into the lungs of recipient BALB/c mice (I-a(d)) induced the histology and immunology of acute lung allograft rejection. Using this model, the purpose of the current study was to determine the role of ICAM-1 on donor lung cells in lung allograft rejection.


METHODS
BALB/c mice received allogeneic BAL cells from wild-type or ICAM-1 mutant (lacking ICAM-1 expression) C57BL/6 mice by nasal insufflation weekly for 4 weeks. Recipient mice underwent BAL and serum collection for the determination of T helper 1/T helper 2 cytokines and IgG subtypes. Lung histology was graded using standard criteria for allograft rejection.


RESULTS
Although wild-type cells induced a lymphocytic vasculitis and bronchitis, ICAM-1 mutant allogeneic BAL cells only induced a lymphocytic vasculitis in recipient lungs. Both wild-type and ICAM-1 mutant cells induced up-regulated local interferon-gamma and IgG2a production, and deposition of IgG2a in recipient lungs.


CONCLUSIONS
These data show that ICAM-1 on donor lung accessory cells mediates differential effects on the histology and immunology of acute lung allograft rejection.
Wilkes
D S
DS
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA. dwilkes@iupui.edu
Bowman
D
D
Cummings
O W
OW
Heidler
K M
KM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D006084:Graft Rejection; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000473:pathology; D016040:Lung Transplantation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous
D007074:Immunoglobulin G; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma