Analysis of leukocyte activation during acute rejection of pulmonary allografts in noninfected and cytomegalovirus-infected rats.
After human lung transplantation acute rejection and cytomegalovirus (CMV) infections may occur, probably contributing to the development of chronic rejection. We established a model of subacute allograft rejection in rats to analyze leukocyte activation and effects of a CMV infection. Histoincompatible lung transplants (BN/LEW) without immunosuppression (group A) and lungs of initially immunosuppressed animals (group B) were analyzed. The production of inflammatory mediators (interleukin-6, tumor necrosis factor alpha, nitric oxides) and the expression of MHC class II antigens by alveolar and lung tissue macrophages were significantly enhanced during the alloresponse. In recipients without immunosuppression (group A) allograft necrosis was detected by day 6, whereas group B allografts were fully rejected by day 25. In allografts of immunosuppressed, CMV-infected animals (group C) the CMV infection was clearly aggravated and the number of activated lung tissue macrophages was increased when compared with noninfected allografts or isografts. The subacute model provides the advantage of allowing us to study mechanisms of acute rejection without the effects of reperfusion injury. Furthermore these findings underline the role of inflammatory mediators produced by macrophages during rejection.
Steinmüller
C
C
Department of Immunobiology, Fraunhofer Institute, Hannover, Germany.
Steinhoff
G
G
Bauer
D
D
You
X M
XM
Denzin
H
H
Franke-Ullmann
G
G
Hausen
B
B
Bruggemann
C
C
Wagner
T O
TO
Lohmann-Matthes
M L
ML
Emmendörffer
A
A
D000208:Acute Disease; D000818:Animals; D018893:Bronchoalveolar Lavage; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control / Q000821:virology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D016040:Lung Transplantation / Q000276:immunology*; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide