Intracoronary E-/L-selectin blockade reduces neutrophil infiltration in heart transplantation.
BACKGROUND
This study examined the effect of local intracoronary delivery of a unique monoclonal antibody (mAb) to both E- and L-selectin (EL-246) on neutrophil infiltration after global ischemia during cardiac transplantation.


METHODS
In 12 ovine heart transplants, allograft coronary arteries were locally perfused with EL-246 (n = 6), or isotype-matched control antibodies (n = 2) or saline (n = 4). At 24 hours posttransplant, myocardium was analyzed for neutrophil infiltration and myocardial water content.


RESULTS
The mean number of intramyocardial neutrophils per area (PMN/hpf) was greatly reduced in the allografts perfused with EL-246 (3.45 +/- 0.4 PMN/hpf), compared with an average 6.5 +/- 0.97 PMN/hpf in control hearts (p = 0.004). Peripheral leukocyte counts were unaffected; myocardial water content was not significantly reduced.


CONCLUSIONS
Local perfusion of cardiac allografts with blocking antibody EL-246 before reperfusion significantly reduced the neutrophilic infiltration that occurs early after transplantation. Prohibiting neutrophil-endothelial adhesion and transmigration may be useful in decreasing neutrophil-dependent post-reperfusion injury in transplantation and routine cardiac surgery.
Carter
Yvonne M
YM
Department of Surgery, University of Washington, Seattle, Washington, USA.
Thomas
Robert
R
Bargatze
Robert
R
Poppa
Veronica
V
Jutila
Mark
M
Murry
Charles E
CE
Allen
Margaret D
MD
D000818:Animals; D000911:Antibodies, Monoclonal; D019040:E-Selectin / Q000276:immunology*; D016027:Heart Transplantation / Q000473:pathology*; D019041:L-Selectin / Q000276:immunology*; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D009504:Neutrophils / Q000473:pathology*; D012756:Sheep; D014867:Water / Q000032:analysis
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D014867:Water; D019041:L-Selectin