Mechanism of hemolysis of human erythrocytes exposed to monosodium urate monohydrate crystals. Preliminary characterization of membrane pores.
Microcrystals of monosodium urate monohydrate (MSUM) have the ability to cause rapid hemolysis of erythrocytes. The nature of the initial MSUM crystal-erythrocyte membrane binding interaction was investigated over a range of different ionic strength media. There was negligible binding of MSUM to erythrocyte ghost membranes in low ionic strength media such as isotonic mannitol but binding was dramatically increased in isotonic NaCl/mannitol solutions or isotonic mannitol containing 1 mM Ca2+. Hemolysis induced by MSUM crystals was preceded by the leakage of K+ from the cells suggesting a colloid-osmotic mechanism of hemolysis. The inclusion of large (oligosaccharide) molecules in the extracellular media or the modulation of the extracellular solution tonicity inhibited both the rate and extent of hemolysis supporting the concept of MSUM-induced pores followed by colloid osmotic hemolysis.
Jackson
J K
JK
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Winternitz
C I
CI
Burt
H M
HM
D002021:Buffers; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000648:ultrastructure*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D006982:Hypertonic Solutions; D007700:Kinetics; D008353:Mannitol / Q000494:pharmacology; D009994:Osmolar Concentration; D010710:Phosphates / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D014527:Uric Acid / Q000378:metabolism / Q000494:pharmacology*
D002021:Buffers; D002413:Cations, Divalent; D006982:Hypertonic Solutions; D010710:Phosphates; D014527:Uric Acid; D008353:Mannitol; D012965:Sodium Chloride; D011188:Potassium; D002118:Calcium