Inhibition of the adherence of T-lymphocytes to epithelial cells by a cyclic peptide derived from inserted domain of lymphocyte function-associated antigen-1.
Tissue inflammation is characterized by aggravated leukocyte infiltration into the sites of inflammation. The mechanism requires the interactions of leukocyte adhesion-molecules and their ligands in the inflamed tissues. In this study, we demonstrate that a cyclic peptide cLAB.L [cyclol, 12-PenlTDGEATDSGC], derived from the "inserted" or I-domain of LFA-1 is able to inhibit the adherence of T-lymphocytes to the epithelial cell monolayers. This inhibition has been thought to involve the disruption of LFA-1/ICAM-1 interaction. The heterotypic adhesion of phorbol ester-activated Molt-3 cells and IFN-gamma-induced Caco-2 monolayers was inhibited upon treatment of the monolayers with monoclonal antibodies (MAbs) to adhesion molecules or with cLAB.L peptide. The adhesion can be inhibited by MAbs to ICAM-1, ICAM-2, and VCAM-1, and cLAB.L peptide in a concentration-dependent manner. However, none of the individual uses of these molecules led to a total inhibition. The inhibitory activity of cLAB.L is greatly reduced by low temperature and the absence of cell activation. Treatment of cLAB.L peptide may trigger an early event of apoptosis on activated but not on non-activated Molt-3 cells; no indication of peptide-induced apoptosis was found on Caco-2 cells. Taken together, data from this work suggest that cLAB.L may have applications to direct cell-targeted delivery during tissue inflammation.
Yusuf-Makagiansar
H
H
Department of Pharmaceutical Chemsitry, The University of Kansas, Lawrence 66047, USA.
Makagiansar
I T
IT
Siahaan
T J
TJ
D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000209:etiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D013696:Temperature
D016169:Lymphocyte Function-Associated Antigen-1; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; C438958:cyclo(l,12-PenlTDGEATDSGC); C103774:glycyl-arginyl-glycyl-aspartyl-asparaginyl-proline; D018799:Intercellular Adhesion Molecule-1