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Alpha L-integrin I domain cyclic peptide antagonist selectively inhibits T cell adhesion to pancreatic islet microvascular endothelium.
Am J Physiol Gastrointest Liver Physiol. 2005 Jan; 288(1):G67-73.AJ

Abstract

Insulitis is a hallmark feature of autoimmune diabetes that ultimately results in islet beta-cell destruction. We examined integrin requirements and specific inhibition of integrin structure in T cell and monocyte adhesion to pancreatic islet endothelium. Examination of cell surface integrin expression on WEHI 7.1 T cells revealed prominent expression of beta-, beta(1)-, alpha(L)-integrins, and low expression of alpha(M)-integrins; whereas WEHI 274.1 monocytes showed significant staining for beta(2)-, beta(1)-, alpha(M)-molecules and no expression of alpha(L)-molecules. Unstimulated islet endothelium showed constitutive levels of ICAM-1 counter-ligand expression with minimal VCAM-1 expression; however, TNF-alpha stimulation increased cell surface density of both molecules. TNF-alpha increased T cell and monocyte rolling and adhesion under hydrodynamic flow conditions. Administration of a cyclic peptide competitor for the alpha(L)-integrin I domain binding sites (cyclo1,12-PenITDGEATDSGC) blocked T cell adhesion without inhibiting monocyte adhesion. Examination of T cell rolling revealed that cLAB.L treatment increased the average rolling velocity on activated endothelium and significantly decreased the fraction of T cells rolling at < or =50 microm/s, suggesting that cLAB.L treatment interferes with signal activation events required for the conversion of T cell rolling to firm adhesion. These data demonstrate for the first time that cyclic peptide antagonists against alpha(L)-integrin I domain attenuate T cell recruitment to islet endothelium.

Authors+Show Affiliations

Dept. of Pathology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA 71130, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

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

15319185

Citation

Huang, Meng, et al. "Alpha L-integrin I Domain Cyclic Peptide Antagonist Selectively Inhibits T Cell Adhesion to Pancreatic Islet Microvascular Endothelium." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 288, no. 1, 2005, pp. G67-73.
Huang M, Matthews K, Siahaan TJ, et al. Alpha L-integrin I domain cyclic peptide antagonist selectively inhibits T cell adhesion to pancreatic islet microvascular endothelium. Am J Physiol Gastrointest Liver Physiol. 2005;288(1):G67-73.
Huang, M., Matthews, K., Siahaan, T. J., & Kevil, C. G. (2005). Alpha L-integrin I domain cyclic peptide antagonist selectively inhibits T cell adhesion to pancreatic islet microvascular endothelium. American Journal of Physiology. Gastrointestinal and Liver Physiology, 288(1), G67-73.
Huang M, et al. Alpha L-integrin I Domain Cyclic Peptide Antagonist Selectively Inhibits T Cell Adhesion to Pancreatic Islet Microvascular Endothelium. Am J Physiol Gastrointest Liver Physiol. 2005;288(1):G67-73. PubMed PMID: 15319185.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha L-integrin I domain cyclic peptide antagonist selectively inhibits T cell adhesion to pancreatic islet microvascular endothelium. AU - Huang,Meng, AU - Matthews,Kametra, AU - Siahaan,Teruna J, AU - Kevil,Christopher G, Y1 - 2004/08/19/ PY - 2004/8/21/pubmed PY - 2005/3/9/medline PY - 2004/8/21/entrez SP - G67 EP - 73 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 288 IS - 1 N2 - Insulitis is a hallmark feature of autoimmune diabetes that ultimately results in islet beta-cell destruction. We examined integrin requirements and specific inhibition of integrin structure in T cell and monocyte adhesion to pancreatic islet endothelium. Examination of cell surface integrin expression on WEHI 7.1 T cells revealed prominent expression of beta-, beta(1)-, alpha(L)-integrins, and low expression of alpha(M)-integrins; whereas WEHI 274.1 monocytes showed significant staining for beta(2)-, beta(1)-, alpha(M)-molecules and no expression of alpha(L)-molecules. Unstimulated islet endothelium showed constitutive levels of ICAM-1 counter-ligand expression with minimal VCAM-1 expression; however, TNF-alpha stimulation increased cell surface density of both molecules. TNF-alpha increased T cell and monocyte rolling and adhesion under hydrodynamic flow conditions. Administration of a cyclic peptide competitor for the alpha(L)-integrin I domain binding sites (cyclo1,12-PenITDGEATDSGC) blocked T cell adhesion without inhibiting monocyte adhesion. Examination of T cell rolling revealed that cLAB.L treatment increased the average rolling velocity on activated endothelium and significantly decreased the fraction of T cells rolling at < or =50 microm/s, suggesting that cLAB.L treatment interferes with signal activation events required for the conversion of T cell rolling to firm adhesion. These data demonstrate for the first time that cyclic peptide antagonists against alpha(L)-integrin I domain attenuate T cell recruitment to islet endothelium. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/15319185/Alpha_L_integrin_I_domain_cyclic_peptide_antagonist_selectively_inhibits_T_cell_adhesion_to_pancreatic_islet_microvascular_endothelium_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00267.2004?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -