Induction of lymphocyte apoptosis in a murine model of acute lung injury--modulation by lipid emulsions.
Acute lung injury (ALI) and sepsis are the major causes of mortality in intensive care units. Lymphocytes apoptosis is a hallmark feature of late detrimental sepsis. Parenteral nutrition in critically ill patients is based on lipid emulsions, but the impact of ALI and lipid emulsions on lymphocytes has not been defined. The effects of intravenously infused conventional soybean oil (SO)-based and new olive oil (OO)-based emulsions on splenic and blood lymphocytes were investigated in a murine model of endotoxin-induced ALI. After LPS challenge and infusion of lipid emulsions, apoptosis of lymphocytes and lung injury were assessed by flow cytometry, Western blot, and histology. Induction of ALI led to a time-dependent decline in splenic and circulating lymphocyte numbers and an increase in apoptosis, with engagement of the extrinsic apoptotic pathway. Both SO- and OO-based emulsions promoted the apoptosis of splenic lymphocytes before induction of ALI. The OO-based emulsions exhibited lower proapoptotic activity than did SO-based emulsions, an observation paralleled by the induction of survival factors. Induction of ALI increased the mortality of mice receiving SO-based emulsions compared with OO-based emulsions and normal saline. Splenic lymphocyte apoptosis is apparent in murine ALI, which may be linked to detrimental outcome. Infusion of lipid emulsions per se provoked splenic lymphocyte apoptosis. Infusion of SO-based emulsions further augmented the apoptosis of splenic and circulating lymphocytes in ALI and led to increased mortality in mice. These findings may be of relevance for patients experiencing ALI that require parenteral nutrition.
Bi
Ming Hua
MH
University of Giessen Lung Center (UGLC), Justus-Liebig-University of Giessen, Germany.
Ott
Juliane
J
Fischer
Tobias
T
Hecker
Matthias
M
Dietrich
Hartmut
H
Schaefer
Martina Barbara
MB
Markart
Philip
P
Wang
Bao En
BE
Seeger
Werner
W
Mayer
Konstantin
K
D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology* / Q000401:mortality; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004195:Disease Models, Animal; D004655:Emulsions / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000069463:Olive Oil; D010288:Parenteral Nutrition; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology; D013024:Soybean Oil / Q000737:chemistry / Q000494:pharmacology
D004655:Emulsions; D008070:Lipopolysaccharides; D000069463:Olive Oil; D010938:Plant Oils; D013024:Soybean Oil