title: Increased apoptosis in lamina propria B cells during polymicrobial sepsis is FasL but not endotoxin mediated.
abstract: Recent studies from our laboratory demonstrated that mucosal lymphoid tissue such as Peyer's patch cells and lamina propria (LP) B lymphocytes from mice shows evidence of increased apoptosis after sepsis that is associated with localized inflammation/activation. The mechanism for this is poorly understood. Endotoxin as well as Fas/Fas ligand (FasL) have been shown to augment lymphocyte apoptosis; however, their contribution to the increase of apoptosis in LP B-cells during sepsis is not known. To study this, sepsis was induced by cecal ligation and puncture (CLP) in endotoxin-tolerant C3H/HeJ or FasL-deficient C3H/HeJ-FasL(gld) (FasL(-)) mice and LP lymphocytes were isolated 24 h later. Phenotypic, apoptotic, and functional indexes were assessed. The number of LP B cells decreased markedly in C3H/HeJ mice but not in FasL-deficient animals at 24 h after CLP. This was associated with comparable alteration in apoptosis and Fas antigen expression in the B cells of these mice. Septic LP lymphocytes also showed increased IgA production, which was absent in the FasL-deficient CLP mice. Furthermore, Fas ligand deficiency appeared to improve survival of septic challenge. These data suggest that the increase in B cell apoptosis in septic animals is partially due to a Fas/FasL-mediated process but not endotoxin.
authors: Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, 227 Middle House, 593 Eddy St., Providence, RI 02903, USA.
authors: C S
authors: CS
authors: Chung
authors: W
authors: W
authors: Wang
authors: I H
authors: IH
authors: Chaudry
authors: A
authors: A
authors: Ayala
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001402:B-Lymphocytes / Q000473:pathology* / Q000502:physiology; D002432:Cecum; D003238:Connective Tissue / Q000473:pathology* / Q000503:physiopathology; D004731:Endotoxins / Q000633:toxicity*; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D007082:Ileum; D007249:Inflammation; D007413:Intestinal Mucosa / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D018805:Sepsis / Q000473:pathology / Q000503:physiopathology*
chemical_list: D004731:Endotoxins; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins