title: Crystal-induced inflammation: studies of the mechanism of crystal-membrane interactions.
abstract: Studies of the interactions of monosodium urate monohydrate (MSUM) crystals and calcium pyrophosphate dihydrate triclinic (CPPD) crystals with biomembranes have been reviewed. Crystal-membrane binding and crystal-induced membranolysis have been studied using human erythrocytes as a model membrane system. The extent of MSUM-membrane binding was determined by incorporating a hydrophobic, fluorescent probe into the membranes, centrifugation to separate free membranes from membranes with bound crystals and quantitation of free membranes by measuring the total fluorescence intensity. The ability of MSUM and CPPD to hemolyse red cells was used as a measure of the membranolytic potential of the crystals. Fluorescence polarization studies showed that MSUM-membrane binding resulted in fluidization of the membrane. Cross-linking of the membrane proteins of the erythrocyte or the presence of divalent cations in the incubation medium inhibited MSUM induced hemolysis. These findings were explained by hypothesizing a "pore" model mechanism for MSUM induced membranolysis as follows. Binding of crystals to membranes induces the redistribution of transmembrane proteins into clusters or aggregates leading to "pore" formation. The "pores" permit the leakage of low molecular weight soluble compounds and ions acoss the membrane which is followed by osmotic rupture of the membrane.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: H M
authors.initials: HM
authors.lastname: Burt
authors.forename: J K
authors.initials: JK
authors.lastname: Jackson
authors.forename: W
authors.initials: W
authors.lastname: Wu
mesh_terms: D001168:Arthritis / Q000209:etiology* / Q000473:pathology; D002131:Calcium Pyrophosphate / Q000633:toxicity*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000648:ultrastructure*; D006461:Hemolysis; D006801:Humans; D008560:Membrane Fluidity; D008565:Membrane Proteins / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D002131:Calcium Pyrophosphate