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Lipocalin‐2 Regulates the Inflammatory Response During Ischemia and Reperfusion of the Transplanted Heart
Author(s) -
Aigner F.,
Maier H. T.,
Schwelberger H. G.,
Wallnöfer E. A.,
Amberger A.,
Obrist P.,
Berger T.,
Mak T.W.,
Maglione M.,
Margreiter R.,
Schneeberger S.,
Troppmair J.
Publication year - 2007
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2006.01723.x
Subject(s) - medicine , downregulation and upregulation , lipocalin , inflammation , heart transplantation , ischemia , transplantation , reperfusion injury , kidney , apoptosis , endocrinology , biology , biochemistry , gene
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.