RANTES chemokine expression is related to acute cardiac cellular rejection and infiltration by CD45RO T-lymphocytes and macrophages.
BACKGROUND
Despite the advances made in immunosuppression therapy, episodes of acute cellular rejection may affect graft function and survival. We investigated the role of RANTES in cellular recruitment and in cardiac allograft rejection.


METHODS
Endomyocardial biopsies (n = 65) from 30 patients were taken at various times after transplantation. In 4 subjects who died of acute cellular rejection, the profile of RANTES expression was monitored in all biopsy specimens and in postmortem tissue. Myocardial tissue from 10 other transplants was also analyzed. Sections were stained with an anti-human RANTES antibody with the streptavidin-biotin technique. RANTES-positive cells were related to macrophage, CD45RO "memory" T-cell, and eosinophil infiltration.


RESULTS
RANTES-positive cells were identified within the cellular infiltrate in 95% of biopsies with moderate/severe rejection and 28% with mild rejection. RANTES-positive, CD45RO-positive, and macrophage cell numbers were higher in subjects who died of acute cellular rejection than of other causes. A highly significant difference in RANTES-positive cell number was observed between moderate/severe, mild, and nonrejection groups (p = .0001) and correlated significantly with macrophage number in both right and left ventricles (r = .693, p < .01; r = .599, p < .05, respectively) and with the number of "memory" T cells (r = .829, p < .001; r = .779, p < .01, respectively).


CONCLUSIONS
These findings suggest that local release of RANTES is important in the recruitment of both macrophages and CD45RO T cells in cardiac allograft rejection. RANTES may be an important chemokine to target for therapeutic intervention in heart rejection.
School of Biological Sciences, Manchester University, England, UK.
M
M
Azzawi
P S
PS
Hasleton
P J
PJ
Geraghty
N
N
Yonan
P
P
Krysiak
A
A
El-Gammal
A K
AK
Deiraniya
I V
IV
Hutchinson
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D018946:Chemokine CCL5 / Q000032:analysis / Q000502:physiology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008264:Macrophages / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018946:Chemokine CCL5; D017493:Leukocyte Common Antigens; C067980:CD68 antigen, human; D000097382:CD68 Molecule