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EC3, a heterodimeric disintegrin from Echis carinatus, inhibits human and murine alpha4 integrin and attenuates lymphocyte infiltration of Langerhans islets in pancreas and salivary glands in nonobese diabetic mice.
Biochem Biophys Res Commun. 2000 Jan 07; 267(1):413-7.BB

Abstract

The venom of Echis carinatus suchoreki contains a monomeric disintegrin echistatin (Mr 5,500 Da) that strongly inhibits alphaIIbbeta3, alphavbeta3, and alpha5beta1 integrins and a heterodimeric disintegrin called EC3 (M(r) 14,762 Da). At nanomolar concentration, EC3 inhibits adhesion of human cell lines expressing alpha4beta1 and alpha4beta7 to immobilized VCAM-1; it has a lower inhibitory effect on alpha5beta1-mediated cell adhesion. In this study, we demonstrated that EC3, in contrast to echistatin, inhibited binding of monoclonal anti-alpha4 and anti-alpha5 antibodies to cells expressing alpha4beta7. In a dose-dependent manner and to the same extent, EC3 inhibited adhesion of Jurkat cells and murine splenic lymphocytes to immobilized VCAM-1, whereas echistatin was not active. EC3 injected intraperitoneally into nonobese diabetic (NOD mice) suppressed development of insulitis and sialoadenitis, whereas echistatin had no significant effect. We propose that the effect of EC3 is mediated, at least, in part, by blocking alpha4beta1 and alpha4beta7 on murine lymphocytes.

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Authors+Show Affiliations

Brando C
Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania, 19140, USA.
Marcinkiewicz C
No affiliation info available
Goldman B
No affiliation info available
McLane MA
No affiliation info available
Niewiarowski S
No affiliation info available

MeSH

Amino Acid SequenceAnimalsAntigens, CDCell AdhesionDiabetes Mellitus, Type 1DisintegrinsHumansIntegrin alpha4Intercellular Signaling Peptides and ProteinsIslets of LangerhansJurkat CellsLymphocytesMiceMice, Inbred NODMolecular Sequence DataPeptidesSalivary GlandsSequence AlignmentSequence Homology, Amino AcidSpleenTumor Cells, CulturedViper Venoms

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10623633

Citation

Brando, C, et al. "EC3, a Heterodimeric Disintegrin From Echis Carinatus, Inhibits Human and Murine Alpha4 Integrin and Attenuates Lymphocyte Infiltration of Langerhans Islets in Pancreas and Salivary Glands in Nonobese Diabetic Mice." Biochemical and Biophysical Research Communications, vol. 267, no. 1, 2000, pp. 413-7.
Brando C, Marcinkiewicz C, Goldman B, et al. EC3, a heterodimeric disintegrin from Echis carinatus, inhibits human and murine alpha4 integrin and attenuates lymphocyte infiltration of Langerhans islets in pancreas and salivary glands in nonobese diabetic mice. Biochem Biophys Res Commun. 2000;267(1):413-7.
Brando, C., Marcinkiewicz, C., Goldman, B., McLane, M. A., & Niewiarowski, S. (2000). EC3, a heterodimeric disintegrin from Echis carinatus, inhibits human and murine alpha4 integrin and attenuates lymphocyte infiltration of Langerhans islets in pancreas and salivary glands in nonobese diabetic mice. Biochemical and Biophysical Research Communications, 267(1), 413-7.
Brando C, et al. EC3, a Heterodimeric Disintegrin From Echis Carinatus, Inhibits Human and Murine Alpha4 Integrin and Attenuates Lymphocyte Infiltration of Langerhans Islets in Pancreas and Salivary Glands in Nonobese Diabetic Mice. Biochem Biophys Res Commun. 2000 Jan 7;267(1):413-7. PubMed PMID: 10623633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - EC3, a heterodimeric disintegrin from Echis carinatus, inhibits human and murine alpha4 integrin and attenuates lymphocyte infiltration of Langerhans islets in pancreas and salivary glands in nonobese diabetic mice. AU - Brando,C, AU - Marcinkiewicz,C, AU - Goldman,B, AU - McLane,M A, AU - Niewiarowski,S, PY - 2000/1/7/pubmed PY - 2000/1/7/medline PY - 2000/1/7/entrez SP - 413 EP - 7 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 267 IS - 1 N2 - The venom of Echis carinatus suchoreki contains a monomeric disintegrin echistatin (Mr 5,500 Da) that strongly inhibits alphaIIbbeta3, alphavbeta3, and alpha5beta1 integrins and a heterodimeric disintegrin called EC3 (M(r) 14,762 Da). At nanomolar concentration, EC3 inhibits adhesion of human cell lines expressing alpha4beta1 and alpha4beta7 to immobilized VCAM-1; it has a lower inhibitory effect on alpha5beta1-mediated cell adhesion. In this study, we demonstrated that EC3, in contrast to echistatin, inhibited binding of monoclonal anti-alpha4 and anti-alpha5 antibodies to cells expressing alpha4beta7. In a dose-dependent manner and to the same extent, EC3 inhibited adhesion of Jurkat cells and murine splenic lymphocytes to immobilized VCAM-1, whereas echistatin was not active. EC3 injected intraperitoneally into nonobese diabetic (NOD mice) suppressed development of insulitis and sialoadenitis, whereas echistatin had no significant effect. We propose that the effect of EC3 is mediated, at least, in part, by blocking alpha4beta1 and alpha4beta7 on murine lymphocytes. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/10623633/EC3_a_heterodimeric_disintegrin_from_Echis_carinatus_inhibits_human_and_murine_alpha4_integrin_and_attenuates_lymphocyte_infiltration_of_Langerhans_islets_in_pancreas_and_salivary_glands_in_nonobese_diabetic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(99)91897-1 DB - PRIME DP - Unbound Medicine ER -