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Titolo:
Liposome-induced pulmonary hypertension: properties and mechanism of a complement-mediated pseudoallergic reaction
Autore:
Szebeni, J; Baranyi, L; Savay, S; Bodo, M; Morse, DS; Basta, M; Stahl, GL; Bunger, R; Alving, CR;
Indirizzi:
Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Membrane Biochem, Washington, DC 20307 USA Walter Reed Army Med Ctr Washington DC USA 20307 Washington, DC 20307 USA Natl Stroke Prevent Fdn, Bethesda, MD 20814 USA Natl Stroke Prevent Fdn Bethesda MD USA 20814 Fdn, Bethesda, MD 20814 USA Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Anesthesia, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 & Reperfus Injury, Boston, MA 02115 USA NINDS, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA NINDS Bethesda MDUSA 20892 lepsy Res Branch, NIH, Bethesda, MD 20892 USA Uniformed Serv Univ Hlth Sci, Dept Physiol, Bethesda, MD 20814 USA Uniformed Serv Univ Hlth Sci Bethesda MD USA 20814 Bethesda, MD 20814 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
fascicolo: 3, volume: 279, anno: 2000,
pagine: H1319 - H1328
SICI:
0363-6135(200009)279:3<H1319:LPHPAM>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTI-CHOLESTEROL ANTIBODIES; ENCAPSULATED HEMOGLOBIN; IN-VITRO; ALTERNATIVE PATHWAY; ACTIVATION; ANAPHYLATOXINS; AMPHOTERICIN; DOXORUBICIN; INHIBITION; IMMUNITY;
Keywords:
hypersensitivity reactions; anaphylatoxin; hemoglobin; IgM-enriched intravenous immunoglobulin; hemodynamics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Szebeni, J Walter Reed Army Inst Res, Dept Membrane Biochem, 503 Robert Grant Rd, Silver Spring, MD 20910 USA Walter Reed Army Inst Res 503 Robert Grant Rd Silver Spring MD USA 20910
Citazione:
J. Szebeni et al., "Liposome-induced pulmonary hypertension: properties and mechanism of a complement-mediated pseudoallergic reaction", AM J P-HEAR, 279(3), 2000, pp. H1319-H1328

Abstract

Intravenous injection of liposomes can cause significant pulmonary hypertension in pigs, a vasoconstrictive response that provides a sensitive model for the cardiopulmonary distress in humans caused by some liposomal drugs. The reaction was recently shown to be a manifestation of "complement activation-related pseudoallergy" (CARPA; Szebeni J, Fontana JL, Wassef NM, Mongan PD, Morse DS, Dobbins DE, Stahl GL, Bunger R, and Alving CR. Circulation 99: 2302-2309, 1999). In the present study we demonstrate that the composition, size, and administration method of liposomes have significant influence on pulmonary vasoactivity, which varied between instantaneously lethal (following bolus injection of 5 mg lipid) to nondetectable (despite infusion of a 2,000-fold higher dose). Experimental conditions augmenting the pulmonary hypertensive response included the presence of dimyristoyl phosphatidylglycerol, 71 mol% cholesterol, distearoyl phosphatidylcholine, and hemoglobin in liposomes, increased vesicle size and polydispersity, and bolus injection vs. slow infusion. The vasoactivity of large multilamellar liposomes was reproduced with human C3a, C5a, and xenoreactive immunoglobulins, and itcorrelated with the complement activating and natural antibody binding potential of vesicles. Unilamellar, monodisperse liposomes with 0.19 +/- 0.10 mm mean diameter had no significant vasoactivity. These data indicate that liposome-induced pulmonary hypertension in pigs is multifactorial, it is due to natural antibody-triggered classic pathway complement activation and it can be prevented by appropriate tailoring of the structure and administration method of vesicles.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 02:46:27