Mild hyperthermia down-regulates receptor-dependent neutrophil function.
Mild hypothermia impairs resistance to infection and, reportedly, impairs phagocytosis and oxidative killing of unopsonized bacteria. We evaluated various functions at 33 degrees-41 degrees C in neutrophils taken from volunteers. Adhesion on endothelial cells was determined using light microscopy. Adhesion molecule expression and receptors, phagocytosis, and release of reactive oxidants were assessed using flow cytometric assays. Adhesion protein CD11b expression on resting neutrophils was temperature-independent. However, up-regulation of CD11b with tumor necrosis factor (TNF)-alpha was increased by hypothermia and decreased with hyperthermia. Neutrophil adhesion to either resting or activated endothelial cells was not temperature-dependent. Bacterial uptake was inversely related to temperature, more so with Escherichia coli than Staphylococcus aureus. Temperature dependence of phagocytosis occurred only wi thopsonized bacteria. Hypothermia slightly increased N-formyl-L-methionyl-L-leucyl-phenylalanine receptors on neutrophils: hyperthermia decreased expression, especially with TNF-alpha. N-formyl-L-methionyl-L-leucyl-phenylalanine-induced H2O2 production was inversely related to temperature, especially in the presence of TNF-alpha. Conversely, phorbol-13-myristate-12-acetate, an activator of protein kinase C, induced an extreme and homogenous release of reactive oxidants that increased with temperature. In contrast to nonreceptor-dependent phagocytosis and oxidative killing, several crucial receptor-dependent neutrophil activities show temperature-dependent regulation, with hypothermia increasing function. The temperature dependence of neutrophil function is thus more complicated than previously appreciated.
Departments of *Anesthesia, †Clinical Chemistry and Laboratory Medicine, and ‡Surgery, University of Regensburg, Regensburg, Germany; and §Outcomes Research™ Institute and Departments of Anesthesiology and Pharmacology, University of Louisville, Louisville, Kentucky.
Dieter
D
Fröhlich
Sigrid
S
Wittmann
Gregor
G
Rothe
Daniel I
DI
Sessler
Peter
P
Vogel
Kai
K
Taeger
D000328:Adult; D039481:CD11b Antigen / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology*; D020536:Enzyme Activators / Q000494:pharmacology; D005334:Fever / Q000503:physiopathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D016877:Oxidants / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D016028:Receptors, Leukocyte-Adhesion / Q000187:drug effects; D013696:Temperature; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D039481:CD11b Antigen; D015815:Cell Adhesion Molecules; D020536:Enzyme Activators; D016877:Oxidants; D016028:Receptors, Leukocyte-Adhesion; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate