title: Rough-Form Lipopolysaccharide Increases Apoptosis in Human CD4⁺ and CD8⁺ T Lymphocytes.
abstract: Immunosuppression induced by lymphocyte apoptosis is considered an important factor in the pathogenesis of sepsis and has been demonstrated in both animal models of lipopolysaccharide (LPS)-induced endotoxemia and septic patients. As rough-form LPS (R-LPS) has recently been shown to elicit a stronger immunological response than regular smooth-form LPS (S-LPS), we aimed to assess the apoptosis-inducing capabilities of R-LPS in different subsets of lymphocytes (CD4(+) T cells, CD8(+) T cell, B cells and NK cells). Using multicolour flow cytometry on human peripheral blood mononuclear cells, we found that R-LPS increased apoptosis in CD4(+) and CD8(+) T cells assessed by annexin V and propidium iodide (AV(+) PI(-)), compared with both S-LPS-stimulated and unstimulated cells. 7-Amino-actinomycin D and staining for intracellular active caspase-3, which are considered later signs of apoptosis, did not reveal the same results. Both forms appeared to inhibit apoptosis in B cells, but no LPS-form-specific effect was seen on B or NK cells. Our results indicate that R-LPS induces a stronger AV(+) PI(-)-assessed apoptotic response in T cells than S-LPS. Our findings emphasize the importance of T cell apoptosis in endotoxemia and advocates for control of LPS form in both endotoxemia research and clinical trials with Gram-negative infections.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, DenmarkDepartment of Biochemical Pathology, Aarhus University Hospitals, Aarhus, DenmarkDepartment of Anaesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, SwedenDepartment of Surgery, University of Zurich Hospital, Zurich, Switzerland.
authors.forename: J S
authors.initials: JS
authors.lastname: Nielsen
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, DenmarkDepartment of Biochemical Pathology, Aarhus University Hospitals, Aarhus, DenmarkDepartment of Anaesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, SwedenDepartment of Surgery, University of Zurich Hospital, Zurich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, DenmarkDepartment of Biochemical Pathology, Aarhus University Hospitals, Aarhus, DenmarkDepartment of Anaesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, SwedenDepartment of Surgery, University of Zurich Hospital, Zurich, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Ledet
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, DenmarkDepartment of Biochemical Pathology, Aarhus University Hospitals, Aarhus, DenmarkDepartment of Anaesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, SwedenDepartment of Surgery, University of Zurich Hospital, Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Turina
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, DenmarkDepartment of Biochemical Pathology, Aarhus University Hospitals, Aarhus, DenmarkDepartment of Anaesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, SwedenDepartment of Surgery, University of Zurich Hospital, Zurich, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Tønnesen
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, DenmarkDepartment of Biochemical Pathology, Aarhus University Hospitals, Aarhus, DenmarkDepartment of Anaesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, SwedenDepartment of Surgery, University of Zurich Hospital, Zurich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Krog
mesh_terms: D017304:Annexin A5; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D053148:Caspase 3 / Q000378:metabolism; D002469:Cell Separation; D003609:Dactinomycin / Q000031:analogs & derivatives; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D061251:Primary Cell Culture; D011419:Propidium; D055815:Young Adult
chemical_list: D017304:Annexin A5; D015703:Antigens, CD; D008070:Lipopolysaccharides; D003609:Dactinomycin; D011419:Propidium; C025942:7-aminoactinomycin D; D053148:Caspase 3