Lymphatic injury and regeneration in cardiac allografts.
BACKGROUND
Severed donor heart lymphatics are not anastomosed to recipient lymphatics in cardiac transplantation. We evaluated the effects of cellular infiltrates of T cells and macrophages on the morphology of lymphatics in heart grafts.


METHODS
Dark agouti hearts were transplanted to Lewis or control dark agouti rats on subtherapeutic doses of cyclosporin. Transplants were examined by immunohistology and quantitative immunofluorescence microscopy using lymphatic endothelial hyaluronan receptor-1 as a lymphatic marker and CD8 and CD68 as markers for cellular infiltration at selected intervals from 1 to 8 weeks posttransplantation.


RESULTS
Allograft inner myocardial lymphatic density decreased by more than 30-fold at 1 week and recovered to only 15% of the native level at 8 weeks posttransplantation. In contrast, allograft lymphatics in and near the epicardium showed no significant density decline but increased in size by more than 5-fold at 2 weeks, and sustained approximately 3-fold increase at 8 weeks posttransplantation. Lymphatic changes correlated temporally with the extent of T cell and macrophage infiltration in allografts, which peaked at 2 to 3 weeks posttransplantation. When grafts were retransplanted from allogeneic to isogeneic recipients at 3 weeks posttransplantation, inner lymphatic density returned close to native level within 2 weeks after retransplantation.


CONCLUSIONS
This is the first characterization of regional and morphologic effects of immunologic responses on heart lymphatics after transplantation. Elimination of alloimmune responses produces rapid restoration of inner lymphatic vessels, suggesting that lymphatics injured during rejection can recover when rejection is reversed during the posttransplantation course.
Soong
Thing Rinda
TR
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Pathak
Arvind P
AP
Asano
Hiroshi
H
Fox-Talbot
Karen
K
Baldwin
William M
WM
D000714:Anastomosis, Surgical; D000818:Animals; D001011:Aorta / Q000601:surgery; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology* / Q000502:physiology*; D007519:Isoantigens / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008208:Lymphatic System / Q000473:pathology*; D008297:Male; D011651:Pulmonary Artery / Q000601:surgery; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000032:analysis; D012038:Regeneration / Q000502:physiology*; D016042:Transplantation, Heterotopic / Q000379:methods; D014184:Transplantation, Homologous
D007519:Isoantigens; C533408:Lyve1 protein, rat; D011956:Receptors, Cell Surface