help button home button Am J Pathol ASIP WHAT IS IT?
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fagoonee, S.
Right arrow Articles by Tolosano, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fagoonee, S.
Right arrow Articles by Tolosano, E.
(American Journal of Pathology. 2005;166:973-983.)
© 2005 American Society for Investigative Pathology

Plasma Protein Haptoglobin Modulates Renal Iron Loading

Sharmila Fagoonee*, Jakub Gburek{dagger}{ddagger}, Emilio Hirsch*§, Samuele Marro*, Soren K. Moestrup, Jacob M. Laurberg||, Erik I. Christensen{dagger}, Lorenzo Silengo*§, Fiorella Altruda*§ and Emanuela Tolosano*§

From the Department of Genetics, Biology and Biochemistry,* University of Turin, Turin, Italy; the Experimental Medicine Research Center,§ San Giovanni Battista Hospital, Turin, Italy; the Departments of Cell Biology{dagger} and Medical Biochemistry, University of Aarhus, Aarhus, Denmark; the Department of Pharmaceutical Biochemistry,{ddagger} Wroclaw Medical University, Wroclaw, Poland; and the Department of Cardiology,|| Aarhus University Hospital, Skejby, Denmark

Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme-iron recovery. We used haptoglobin-null mice to evaluate the impact of haptoglobin gene inactivation on iron metabolism. Haptoglobin deficiency led to increased deposition of hemoglobin in proximal tubules of the kidney instead of the liver and the spleen as occurred in wild-type mice. This difference in organ distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
F. Vinchi, S. Gastaldi, L. Silengo, F. Altruda, and E. Tolosano
Hemopexin Prevents Endothelial Damage and Liver Congestion in a Mouse Model of Heme Overload
Am. J. Pathol., July 1, 2008; 173(1): 289 - 299.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
K. Theilgaard-Monch, L. C. Jacobsen, M. J. Nielsen, T. Rasmussen, L. Udby, M. Gharib, P. D. Arkwright, A. F. Gombart, J. Calafat, S. K. Moestrup, et al.
Haptoglobin is synthesized during granulocyte differentiation, stored in specific granules, and released by neutrophils in response to activation
Blood, July 1, 2006; 108(1): 353 - 361.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. J. Schaer, C. A. Schaer, P. W. Buehler, R. A. Boykins, G. Schoedon, A. I. Alayash, and A. Schaffner
CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin
Blood, January 1, 2006; 107(1): 373 - 380.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the American Society for Investigative Pathology.