Heme uptake by endothelium synergizes polymorphonuclear granulocyte-mediated damage.

G. Balla, G. Vercellotti, J. W. Eaton, H. S. Jacob

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20 Citations (Scopus)

Abstract

Transitional metals, particularly iron, markedly potentiate oxidant damage to isolated cell organelles. However, determining the probable importance of iron in damage to intact cells is difficult because of our inability experimentally to increase the cell content of this transition metal. We now report that heme is a uniquely effective iron delivery vehicle, capable of loading large amounts of potentially reactive iron into intact cells. We find that endothelial cells in vitro rapidly incorporate free heme and this heme-loading sensitizes endothelium to oxidant-mediated cytotoxicity caused by hydrogen peroxide, the hypoxanthine/xanthine oxidase system, or phorbol-stimulated PMN. Although the precise mechanism of the heme-aggravated cytotoxicity is not yet known, it closely parallels amplified lipid peroxidation in endothelial cell membranes suggesting the importance of lipid injury. Hemopexin, by complexing heme, protects endothelial cells from activated PMN, but only if added simultaneously. The hydrophobic iron chelator and antioxidant, U74500A, abrogates heme-augmented hydrogen peroxide and PMN-mediated endothelial damage. Such compounds, therefore, may have therapeutic potential in one or more of the listed clinical syndromes. We speculate that exposure of endothelium to free heme may potentiate vascular damage in various clinical syndromes, including acute renal failure after massive intravascular hemolysis, crush injuries, reperfusion after myocardial infarction (perhaps secondary to cardiac myoglobin release), retrolental fibroplasia associated with neonatal hemopexin deficiency, and, perhaps, atherosclerosis involving sites of turbulence that may trigger minor red blood cell lysis.

Original languageEnglish
Pages (from-to)174-179
Number of pages6
JournalTransactions of the Association of American Physicians
Volume103
Publication statusPublished - 1990

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Heme
Granulocytes
Endothelium
Iron
Hemopexin
Endothelial Cells
Oxidants
Hydrogen Peroxide
Metals
Retinopathy of Prematurity
Xanthine Oxidase
Myoglobin
Chelating Agents
Hemolysis
Acute Kidney Injury
Organelles
Lipid Peroxidation
Reperfusion
Blood Vessels
Atherosclerosis

ASJC Scopus subject areas

  • Medicine(all)

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Heme uptake by endothelium synergizes polymorphonuclear granulocyte-mediated damage. / Balla, G.; Vercellotti, G.; Eaton, J. W.; Jacob, H. S.

In: Transactions of the Association of American Physicians, Vol. 103, 1990, p. 174-179.

Research output: Contribution to journalArticle

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