Sepsis induces apoptosis and profound depletion of splenic interdigitating and follicular dendritic cells.
Dendritic cells are a phenotypically diverse group of APC that have unique capabilities to regulate the activity and survival of B and T cells. Although proper function of dendritic cells is essential to host control of invading pathogens, few studies have examined the impact of sepsis on dendritic cells. The purpose of this study was to determine the effect of sepsis on splenic interdigitating dendritic cells (IDCs) and follicular dendritic cells (FDCs) using a clinically relevant animal model. Immunohistochemical staining for FDCs showed that sepsis induced an initial marked expansion in FDCs that peaked at 36 h after onset. The FDCs expanded to fill the entire lymphoid zone otherwise occupied by B cells. Between 36 and 48 h after sepsis, there was a profound caspase 3 mediated apoptosis induced depletion of FDCs such that only a small contingent of cells remained. In contrast to the initial increase in FDCs, IDC numbers were decreased to approximately 50% of control by 12 h after onset of sepsis. IDC death occurred by caspase 3-mediated apoptosis. Such profound apoptosis induced loss of FDCs and IDCs may significantly compromise B and T cell function and impair the ability of the host to survive sepsis.
Tinsley
Kevin W
KW
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Grayson
Mitchell H
MH
Swanson
Paul E
PE
Drewry
Anne M
AM
Chang
Katherine C
KC
Karl
Irene E
IE
Hotchkiss
Richard S
RS
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D053148:Caspase 3; D020169:Caspases / Q000502:physiology; D002432:Cecum; D002452:Cell Count; D020566:Dendritic Cells, Follicular / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D016867:Immunocompromised Host / Q000276:immunology; D007150:Immunohistochemistry; D008026:Ligation; D008264:Macrophages / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011677:Punctures; D018805:Sepsis / Q000276:immunology* / Q000473:pathology*; D013154:Spleen / Q000737:chemistry / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D013194:Staining and Labeling; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology
C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases