Local antilaminin antibody treatment alters the rejection pattern of murine cardiac allografts: correlation between cellular infiltration and extracellular matrix.
BACKGROUND
Emerging data place extracellular matrix (ECM) proteins as important elements in lymphocyte positioning and effector function in alloreactive responses. Using a non-vascularized model of allogeneic heart transplantation in Swiss mice, we have observed a correlation between the cellular infiltration and ECM deposition towards the interior of the graft during the kinetics of rejection.


METHODS
To confirm the importance of ECM during the rejection process in this model, we treated the transplanted animals with local injections of antilaminin monoclonal antibody and analyzed, by histology and immunohistochemistry, the grafts on day 15, which corresponds to the peak of cellular infiltration and ECM deposition.


RESULTS
The treatment with mAb antilaminin decreased the cellular infiltrate and ECM deposition within the grafts, as compared to controls. Moreover, we found a diminished IFN-gamma, TNF-alpha and IL-2 deposition in the transplant area, and a reduced co-localization of these cytokines with laminin. By contrast, the antilaminin treatment increased tenascin deposition, a molecule with immunosuppressive properties, and also caused an increase in apoptosis of the cellular infiltrate.


CONCLUSIONS
These data hallmark the importance of laminin, in distinct aspects concerning the events leading to allograft rejection, and also reinforce this molecule as a potential target for immune intervention in organ transplantation.
Riederer
Ingo
I
Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Silva-Barbosa
Suse D
SD
Rodrigues
Marcio L
ML
Savino
Wilson
W
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000378:metabolism*; D006084:Graft Rejection / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016027:Heart Transplantation; D007797:Laminin / Q000276:immunology*; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D007797:Laminin