Increased susceptibility in Hp knockout mice during acute hemolysis

被引:184
作者
Lim, SK
Kim, HK
Lim, SK
bin Ali, A
Lim, YK
Wang, YP
Chong, SM
Costantini, F
Baumman, H
机构
[1] Natl Univ Med Inst, Cardiovasc Res Inst, Singapore 119260, Singapore
[2] Natl Univ Singapore, Honors Program Biochem, Singapore, Singapore
[3] Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA
[4] Natl Univ Singapore Hosp, Dept Pathol, Singapore, Singapore
[5] Columbia Univ, Dept Genet & Dev, New York, NY USA
关键词
D O I
10.1182/blood.V92.6.1870.418k38_1870_1877
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Haptoglobin, a conserved plasma glycoprotein, forms very stable soluble complexes with free plasma hemoglobin. Hemoglobin binding by haptoglobin is thought to be important in the rapid hepatic clearance of hemoglobin from the plasma and in the inhibition of glomerular filtration of hemoglobin. To evaluate these functions, Haptoglobin knockout (-/-) mice were created. These mice were viable but had a small, significant reduction in postnatal viability. Contrary to popular belief, the lack of haptoglobin did not impair clearance of free plasma hemoglobin in -/- mice. Induction of severe hemolysis by phenylhydrazine caused extensive hemoglobin precipitation in the renal tubular cells of both -/- and +/+ mice, with death occurring in 55% of -/- mice and in 18% of +/+ mice. In general, phenylhydrazine-treated -/- mice suffered greater tissue damage, as evidenced by the induction of hepatic acute phase response resulting in increased plasma alpha 1-acid glycoprotein (AGP) levels. Among -/- and +/+ mice that survived, -/- mice tend to suffer greater oxidative damage and failed to repair or regenerate damaged renal tissues, as indicated by their higher plasma malonaldehyde (MDA) and 4-hydroxy-2(E)-nonenal (HNE) levels and lower mitotic indices in their kidneys, respectively. This study Suggested that a physiologically important role;of hemoglobin-haptoglobin complex formation is the amelioration of tissue damages by hemoglobin-driven lipid peroxidation. (C) 1998 by The American Society of Hematology.
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页码:1870 / 1877
页数:8
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