Induction of cell death in T lymphocytes by invasin via beta1-integrin.
Ligand binding to beta1-integrins exerts multiple effects on cells of the immune system including adhesion, spreading, haptotaxis and costimulation of T cells activated by anti-CD3. Here we show that a high-affinity ligand for beta1-integrins, the invasin (Inv) protein of Yersinia pseudotuberculosis, can induce cell death in T lymphocytes via a rapid process. Partially purified native Inv protein and an Inv fusion protein caused apoptotic/necrotic caspase-independent cell death in T lymphocytes as determined by phosphatidylserine exposure on the cell surface, uptake of propidium iodide, labeling of DNA strand breaks and presence of DNA ladder. Inv-induced cell death was mediated via beta1-integrins as indicated by the fact that Inv bound to the beta1-integrin subunit (CD29), that anti-beta(1)-integrin antibodies blocked Inv-induced cell death and that Inv-induced cell death was absent in two beta1-integrin- cell lines produced by different procedures. Killing via beta1-integrins represents a novel pathway for cell death in T lymphocytes.
Arencibia
Ignacio
I
Department of Clinical Immunology, University of Umeå, Umeå, Sweden. Ignacio.Arencibia@climi.umu.se
Frankel
Gad
G
Sundqvist
Karl-Gösta
KG
D018829:Adhesins, Bacterial; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017304:Annexin A5 / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D001426:Bacterial Proteins / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation; D006801:Humans; D020287:In Situ Nick-End Labeling; D019012:Integrin beta1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D019169:Jurkat Cells / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D009336:Necrosis; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D014407:Tumor Cells, Cultured; D015011:Yersinia pseudotuberculosis / Q000502:physiology*
D018829:Adhesins, Bacterial; D000590:Amino Acid Chloromethyl Ketones; D017304:Annexin A5; D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D015853:Cysteine Proteinase Inhibitors; D019012:Integrin beta1; D011993:Recombinant Fusion Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C053476:invasin, Yersinia