RGDS peptide inhibits activation of lymphocytes and adhesion of activated lymphocytes to human umbilical vein endothelial cells in vitro.
The Arg-Gly-Asp (RGD) motif is known to mediate cell adhesion to several extracellular matrix components as well as cell-cell interactions. In the present study, we investigated whether the RGDS peptide interferes with cell-cell recognition-based events such as allogeneic activation of PBMC and PBMC adhesion to human umbilical vein endothelial cells (HUVEC). We show here for the first time, to our knowledge, that RGDS significantly inhibits adhesion of activated PBMC to HUVEC; in addition, RGDS inhibits PBMC allogenenic activation in human mixed lymphocyte reaction assays. Caspases played a pivotal role in both events, because preventing their activation abolished or strongly reduced the observed inhibitory effect. The RGDS antirecognition effect was strongly increased by pretreatment of HUVEC with RGDS, which affected mostly T lymphocyte adhesion to HUVEC. These results indicate that PBMC allogeneic activation, as well as reciprocal recognition between activated PBMC and endothelial cells, are RGDS-dependent events that occur through a dual effect involving anti-adhesive and caspase-dependent mechanisms. These data suggest a potential role of RGDS in cell-mediated immunity, inflammation and organ transplantation.
Pozzetto
Ubaldo
U
Laboratory of Immunology, Shock Center, IASI, CNR, Rome, Italy. aldopozzetto@hotmail.com
Aguzzi
Maria Simona
MS
Maggiano
Nicola
N
Scala
Enrico
E
Capelli
Arnaldo
A
Castagneto
Marco
M
Capogrossi
Maurizio C
MC
Citterio
Franco
F
Serino
Francesco
F
Facchiano
Antonio
A
D020169:Caspases / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects*; D002450:Cell Communication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D014471:Umbilical Veins
D007155:Immunologic Factors; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D020169:Caspases