Enhanced expression of heat shock proteins in activated polymorphonuclear leukocytes in patients with sepsis.
BACKGROUND
Heat shock proteins (HSPs) in cells, as molecular chaperons, have been reported to regulate cell functions. The objective of this study was to investigate the HSP expression in polymorphonuclear leukocytes (PMNLs) from severe septic patients and the relation between the expression of HSPs and PMNL function.


METHODS
In blood samples from 21 patients with sepsis and serum C-reactive protein levels more than 10 mg/dL, we used flow cytometry to measure expressions of HSP27, HSP60, HSP70, and HSP90; oxidative activity; and levels of apoptosis in PMNLs during sepsis. In in vitro studies, we used cells from 14 healthy volunteers to examine the relation between the expression of HSP70 and PMNL function. Quercetin (30 microM), a suppressor of HSP, and sodium arsenite (100 microM), an inducer of HSP, were used to regulate the expression of HSP70 in PMNLs, and oxidative activity and apoptosis in these cells were measured.


RESULTS
In patients with sepsis, the expressions of HSP27, HSP60, HSP70, and HSP90 and oxidative activity in PMNLs were significantly increased. Apoptosis of these PMNLs was markedly inhibited. In the in vitro studies, administration of sodium arsenite enhanced the expression of HSP70, significantly increased oxidative activity, and inhibited apoptosis. Administration of quercetin before sodium arsenite prevented the expression of HSP70, the increase in oxidative activity, and the inhibition of apoptosis.


CONCLUSIONS
Sepsis causes the enhanced expression of HSPs in activated PMNLs. In PMNLs with enhanced expression of HSP70, oxidative activity is increased and apoptosis is inhibited. The enhanced expression of HSPs may play a role in regulating PMNL function in patients with sepsis.
Hashiguchi
N
N
Department of Traumatology, Osaka University Medical School, Suita-shi, Osaka, Japan. hashiguchi@mx51.tiki.ne.jp
Ogura
H
H
Tanaka
H
H
Koh
T
T
Nakamori
Y
Y
Noborio
M
M
Shiozaki
T
T
Nishino
M
M
Kuwagata
Y
Y
Shimazu
T
T
Sugimoto
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D018053:Arsenites / Q000494:pharmacology; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D011794:Quercetin / Q000494:pharmacology; D018805:Sepsis / Q000097:blood / Q000378:metabolism*; D017670:Sodium Compounds / Q000494:pharmacology
D018053:Arsenites; D006360:Heat-Shock Proteins; D017670:Sodium Compounds; C017947:sodium arsenite; D011794:Quercetin