Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Formation of complement-activating particles in aqueous solutions of Taxol: possible role in hypersensitivity reactions
Autore:
Szebeni, J; Alving, CR; Savay, S; Barenholz, Y; Priev, A; Danino, D; Talmon, Y;
Indirizzi:
Walter Reed Army Inst Res, Dept Membrane Biochem, Silver Spring, MD 20910 USA Walter Reed Army Inst Res Silver Spring MD USA 20910 Spring, MD 20910 USA Hebrew Univ Jerusalem, Hadassah Med Sch, Lab Membrane & Liposome Res, IL-91120 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91120 -91120 Jerusalem, Israel Technion Israel Inst Technol, Dept Chem Engn, IL-32000 Haifa, Israel Technion Israel Inst Technol Haifa Israel IL-32000 L-32000 Haifa, Israel
Titolo Testata:
INTERNATIONAL IMMUNOPHARMACOLOGY
fascicolo: 4, volume: 1, anno: 2001,
pagine: 721 - 735
SICI:
1567-5769(200104)1:4<721:FOCPIA>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOSE INTRAVENOUS CYCLOSPORINE; CREMOPHOR EL; ANAPHYLACTOID REACTIONS; PACLITAXEL; MECHANISM; LIPOSOMES; INFUSION; ANAPHYLATOXINS; CHOLESTEROL; SURFACTANTS;
Keywords:
cancer chemotherapy; drug allergy; micelles; cremophor EL; cryo-TEM; hypersensitivity reactions; IVIG;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Szebeni, J Walter Reed Army Inst Res, Dept Membrane Biochem, Silver Spring, MD 20910 USA Walter Reed Army Inst Res Silver Spring MD USA 20910 20910 USA
Citazione:
J. Szebeni et al., "Formation of complement-activating particles in aqueous solutions of Taxol: possible role in hypersensitivity reactions", INT IMMUNO, 1(4), 2001, pp. 721-735

Abstract

We reported earlier that the anticancer drug paclitaxel (Taxol) activated the complement (C) system in human serum in vitro, raising the possibility that C activation might play a role in the ill-understood hypersensitivity reactions (HSRs) to this drug [J, Natl. Cancer Inst. 90 (1998) 300], In pursuing the mechanism of C activation by Taxol, the present study provided evidence that dilution of the injection concentrate in aqueous solvents led to the formation of micelles and needle-like structures, both of which caused C activation in vitro. Micelles were formed mainly from Cremophor EL (CrEL), the nonionic emulsifier vehicle of paclitaxel, whose level in Taxol infusion exceeded its critical micelle concentration by at Least 400-fold. CrEL micelles were shown by quasi-elastic light scattering and cryo-transmission electron microscopy (cryo-TEM) to be spherical with diameters in the 8-22 nm range; however, de novo formation of 50-300 nm microdroplets followingincubation with human plasma suggested further fundamental structural transformation in blood. The needle-like structures extended to the multimicronrange and were shown by electron diffraction to be crystalline paclitaxel,Taxol-induced C activation was manifested in varying rises of serum C3a-desarg, iC3b and SC5b-9. The causal role of CrEL micelles in C activation wasdemonstrated by the fact that filtration of aqueous solutions of Taxol or pure CrEL via 30-kDa cutoff filters eliminated, while the filter retentate restored C activation. C activation by Taxol was also inhibited by 10 mg/mlhuman immunoglobulin (IVIG). If proven clinically, HSRs to Taxol may represent a hitherto vaguely classified adverse drug reaction recently called C activation-related pseudoallergy (CARPA) [Circulation 99 (1999) 2302]. (C) 2001 Published by Elsevier Science B.V.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/01/21 alle ore 07:48:19