Lipocalin-2 regulates the inflammatory response during ischemia and reperfusion of the transplanted heart.
Ischemia and reperfusion (IR) are known to negatively affect early allograft function following solid organ transplantation. Lipocalin-2 (Lcn-2) has been described as a marker and potential positive modulator of acute inflammation during these processes. Using a heterotopic murine heart transplant model we previously found that IR resulted in a pronounced upregulation of Lcn-2 mRNA in the heart at 12 (22.7-fold increase) and 24 h (9.8-fold increase) of reperfusion. We now confirm this increase at the protein level and provide evidence for infiltrating polymorphonuclear cells as the primary source of Lcn-2 protein. Lcn-2 levels are increased 6.6-fold at 12 h, 11.4-fold at 24 h and 6.4 fold at 48 h after reperfusion. In Lcn-2(-/-) grafts the number of infiltrating granulocytes is reduced by 54% (p < 0.05) at 2 h, 79% (p < 0.01) at 12 h, 72% (p < 0.01) at 24 h and 52% (p < 0.01) at 48 h after reperfusion compared to Lcn-2(+/+) grafts, without any differences in cardiomyocyte apoptosis. These data suggest a function of Lcn-2 in the initiation of the inflammatory response. Moreover, an increase in Lcn-2 is not only restricted to the transplanted heart, but is also observed in the kidney, hinting at a possible involvement of Lcn-2 in the systemic response to IR.
Aigner
F
F
Department of General and Transplant Surgery and Daniel-Swarovski-Research Laboratory, Innsbruck Medical University, Austria. Felix.Aigner@i-med.ac.at
Maier
H T
HT
Schwelberger
H G
HG
Wallnöfer
E A
EA
Amberger
A
A
Obrist
P
P
Berger
T
T
Mak
T W
TW
Maglione
M
M
Margreiter
R
R
Schneeberger
S
S
Troppmair
J
J
D000209:Acute-Phase Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D000818:Animals; D001013:Aorta, Thoracic / Q000601:surgery; D017209:Apoptosis; D002678:Chimera; D016027:Heart Transplantation / Q000502:physiology*; D007249:Inflammation / Q000517:prevention & control*; D000071068:Lipocalin-2; D054834:Lipocalins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D011651:Pulmonary Artery / Q000601:surgery; D011994:Recombinant Proteins / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014185:Transplantation, Isogeneic
D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011994:Recombinant Proteins; C071332:Lcn2 protein, mouse