The absence of constitutive and induced expression of critical cell-adhesion molecules on human cardiac myocytes. Its role in transplant rejection.
Fetal human cardiac myocytes (FHCM) and a cell line derived from FHCM, termed W1, constitutively express low levels of MHC class I antigens and significant levels of ICAM-1 (CD54), and LFA-3 (CD58) but do not express LFA-1 alpha (CD11a), LFA-1 beta (CD18), GMP-140 (CD62), BB1-B7, VCAM-1, and ELAM-1. In vitro incubation of FHCM or the W-1 cell line for varying periods with varying concentrations of IFN-gamma, TNF-alpha, Poly IC, LPS, IL-alpha, IL-1 beta, PMA, PDBu, and supernatant fluids from Con A-activated PBMC or allogeneic MLR cultures failed to induce cell adhesion molecules (CAMs) or costimulatory molecules that are not constitutively expressed on these cells except for MHC class II antigens. In addition, IFN-gamma, Con A, and MLR supernatant fluids (in order of biological activity) not only induced MHC class II antigens but also markedly increased the mean density of expression per cell of MHC class I and ICAM-1. Analysis of the stability of MHC class I/II molecules using agents like brefeldin-A and Western blot analysis of MHC class II molecules suggest that these ligands are very stably expressed on myocytes. Our previous studies have documented the failure of MHC-expressing FHCM to induce an alloproliferative response. The results of the present studies show that this failure is not secondary to the absence of ICAM-1 or LFA-3 or the presence of unstable MHC molecules but is most likely due to the absence of other CAMs/costimulatory molecules that are critically required for inducing allogeneic activation.
Ansari
A A
AA
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322.
Sundstrom
J B
JB
Runnels
H
H
Jensen
P
P
Kanter
K
K
Mayne
A
A
Herskowitz
A
A
D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000502:physiology*; D002461:Cell Line, Transformed; D004355:Drug Stability; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology; D005333:Fetus / Q000166:cytology; D006084:Graft Rejection; D006321:Heart / Q000196:embryology; D016027:Heart Transplantation / Q000276:immunology*; D000949:Histocompatibility Antigens Class II; D006801:Humans; D009206:Myocardium / Q000737:chemistry / Q000166:cytology*; D014471:Umbilical Veins / Q000166:cytology
D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II