title: Macrophages in experimental rat lung isografts and allografts: infiltration and proliferation in situ.
abstract: Alveolar macrophages (AMs) and peribronchial/perivascular macrophages are probably involved in lung allograft damage. We investigate leukocyte infiltration into graft tissue and address the question whether proliferation in situ contributes to macrophage homeostasis and accumulation. Lung transplantation was performed in the Lewis (LEW)-to-LEW and in the Dark Agouti-to-LEW rat strain combination. Graft infiltration by ED1+ and ED2+ (CD163) macrophages was analyzed by immunohistochemistry (IHC) and compared with infiltration by lymphocytes. Cells in the S-phase of the cell cycle were pulse-labeled with BrdU and detected immunohistochemically. Finally, the donor or recipient origin of AMs was determined by IHC and in situ hybridization. ED1+ AMs in allogeneic transplants increased by more than 25-fold from Days 1 to 5. In addition, large, peribronchial/perivascular infiltrates developed containing numerous ED1+ cells. Although AMs in normal rat lungs are CD163-, AMs up-regulated CD163 between Days 4 and 5, reaching maximum values on Day 6. Lymphocytes were less numerous than macrophages. About 16% of the AMs and 10% of the peribronchial/perivascular macrophages were in the S-phase of the cell cycle on Day 2 post-transplantation. No differences in the frequency of BrdU+ macrophages were obvious between isografts and allografts. AMs of donor origin increased in number considerably during allograft rejection. In conclusion, the cellular infiltrate in lung allografts is dominated by macrophages, which exhibit an unusual phenotype and a strong capacity for mitotic self-renewal.
authors.affiliation: Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, and Department of Clinical Chemistry and Molecular Diagnostics, Hospital of the Philipps-University, Marburg, Germany.
authors.forename: Andree
authors.initials: A
authors.lastname: Schmidt
authors.forename: Jochen
authors.initials: J
authors.lastname: Sucke
authors.forename: Gabriele
authors.initials: G
authors.lastname: Fuchs-Moll
authors.forename: Petra
authors.initials: P
authors.lastname: Freitag
authors.forename: Markus
authors.initials: M
authors.lastname: Hirschburger
authors.forename: Andreas
authors.initials: A
authors.lastname: Kaufmann
authors.forename: Holger
authors.initials: H
authors.lastname: Garn
authors.forename: Winfried
authors.initials: W
authors.lastname: Padberg
authors.forename: Veronika
authors.initials: V
authors.lastname: Grau
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D053331:Ectodysplasins / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000502:physiology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous / Q000276:immunology*; D014185:Transplantation, Isogeneic / Q000276:immunology*
chemical_list: D053331:Ectodysplasins