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The effect of fever‐like temperatures on neutrophil signaling
Author(s) -
Salanova Birgit,
Choi Mira,
Rolle Susanne,
Wellner Maren,
Scheidereit Claus,
Luft Friedrich C.,
Kettritz Ralph
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2983fje
Subject(s) - p38 mitogen activated protein kinases , tumor necrosis factor alpha , apoptosis , mapk/erk pathway , microbiology and biotechnology , fibronectin , integrin , protein kinase b , signal transduction , chemotaxis , chemistry , biology , immunology , receptor , biochemistry , extracellular matrix
The effect of fever on neutrophils has not been explored. We tested the hypothesis that fever‐like temperature spikes affect neutrophil signaling and function. Prior 60 min, 42°C heat exposure inhibited p38 MAPK, ERK, PI3‐Kinase/Akt, and NF‐κB activation in TNF‐α‐challenged suspended neutrophils. Using pharmacological inhibitors and an inhibitory peptide transduced into neutrophils by a HIV‐TAT sequence, we found that p38 MAPK and NF‐κB mediate TNF‐α‐mediated delayed apoptosis in suspended neutrophils. Heat exposure (39–42°C) did not affect constitutive apoptosis but abrogated TNF‐α‐delayed apoptosis in these suspended cells. In contrast, adhesion‐dependent functions were not inhibited. Furthermore, we found that heat exposure neither blocked p38 MAPK, ERK, and NF‐κB activation in neutrophils on fibronectin nor prevented delayed apoptosis by TNF‐α when cells interacted with fibronectin. Above and beyond apoptosis, TNF‐α initiated NF‐κB‐dependent gene transcription. Heat exposure blocked this effect in suspended neutrophils but not in neutrophils on fibronectin. Finally, we show that β2‐integrins, which are not necessary for TNF‐α‐induced NF‐κB activation at 37°C, transduce costimulatory signals allowing NF‐κB activation after heat exposure. The effect could protect circulating neutrophils from TNF‐α activation, while not interfering with activation of adherent neutrophils. Fever could make neutrophils more parsimonious.