Rough-Form Lipopolysaccharide Increases Apoptosis in Human CD4+and CD8+T Lymphocytes

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.

Larsson, AndersUppsala universitet,Anestesiologi och intensivvård(Swepub:uu)andla606 (author)
Ledet, T. (author)
Turina, M. (author)
Tonnesen, E. (author)
Krog, J. (author)
Uppsala universitetAnestesiologi och intensivvård (creator_code:org_t)

By the author/editor: Nielsen, J. S.; Larsson, Anders; Ledet, T.; Turina, M.; Tonnesen, E.; Krog, J.

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