Activated polymorphonuclear leukocytes enhance production of leukocyte microparticles with increased adhesion molecules in patients with sepsis.
BACKGROUND
Leukocyte microparticles (MPs) derived from polymorphonuclear leukocytes (PMNLs) have been recently found to be activators of vascular endothelium in vitro. The precise role of leukocyte MPs has not been clarified in patients suffering severe insult. The objective of this study was to evaluate production of leukocyte MPs and expression of adhesion molecules on the MP surface in patients with sepsis.


METHODS
Twenty-one patients with severe infection (fulfilling the criteria of sepsis with serum C-reactive protein > 10 mg/dL) and 21 healthy volunteers were included as study subjects. Production of leukocyte MPs, expression of CD11b on the MPs, and oxidative activity of PMNLs were measured by flow cytometry in the presence and absence of formyl-methionyl-leucyl-phenylalanine. CD11b expression was evaluated according to the MP size (more than, equal to, or less than 1.0 microm). Soluble E-selectin, thrombomodulin, and PMNL elastase were also measured in blood.


RESULTS
Production of leukocyte MPs and superoxide production in PMNLs with and without formyl-methionyl-leucyl-phenylalanine increased significantly in patients with sepsis in comparison with production in normal volunteers. In patients with sepsis, expression of CD11b was also markedly enhanced on MPs less than 1.0 microm in diameter in comparison with expression in control subjects. Levels of soluble E-selectin, thrombomodulin, and PMNL elastase in blood were significantly increased in patients with sepsis. We succeeded in detecting leukocyte MPs visually by fluorescence microscopy.


CONCLUSIONS
Activated PMNLs enhance production of leukocyte MPs with increased adhesion molecules in patients with sepsis. Activated leukocyte MPs may play a role in the pathogenesis of endothelial activation and leukocyte-endothelium interaction in the presence of sepsis.
Fujimi
Satoshi
S
Department of Traumatology, Osaka University Medical School, Osaka, Japan. fujimi@hp-emerg.med.osaka-u.ac.jp
Ogura
Hiroshi
H
Tanaka
Hiroshi
H
Koh
Taichin
T
Hosotsubo
Hideo
H
Nakamori
Yasushi
Y
Kuwagata
Yasuyuki
Y
Shimazu
Takeshi
T
Sugimoto
Hisashi
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D019040:E-Selectin / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D019272:Leukocyte Elastase / Q000097:blood; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D018180:Thrombomodulin / Q000097:blood
D019040:E-Selectin; D016177:Macrophage-1 Antigen; D018180:Thrombomodulin; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019272:Leukocyte Elastase