Effects of proinflammatory cytokines and bacterial toxins on neutrophil rheologic properties.
OBJECTIVE
To examine the changes in neutrophil deformability, aggregation, and adherence in response to stimulation with proinflammatory cytokines and bacterial toxins.


METHODS
Prospective, randomized trial.


METHODS
Research laboratory.


METHODS
Neutrophils isolated from healthy volunteers.


METHODS
Neutrophils were exposed to tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-8, their combination, endotoxin (LPS), lipoteichoic acid (LTA), and staphyloccocal enterotoxin B (SEB). Neutrophil deformability was measured as percent neutrophils filtered through 5-microm diameter filters. Aggregation was measured using a platelet aggregometer. Adherence was determined by examining the binding of neutrophils to albumin-coated latex beads.


RESULTS
Exposure to TNF-alpha and IL-1beta led to significant decreases in neutrophil filterability, which was attenuated by cytochalasin D pretreatment. LPS and LTA also decreased deformability, suggesting that these toxins directly stimulated neutrophils independent of cytokines. IL-8 and SEB did not significantly affect neutrophil deformability. TNF-alpha and LPS were associated with significant neutrophil aggregation, which was inhibited by pretreatment with anti-CD18 antibodies. Neutrophil aggregation was not affected by IL-1beta, LTA, or SEB. TNF-alpha, IL-8, and LPS increased neutrophil adherence, which also was attenuated by pretreatment with anti-CD18 antibodies. IL-1beta, LTA, and SEB did not significantly affect neutrophil adherence.


CONCLUSIONS
Cytokines and bacterial toxins differ in their effects on neutrophil deformability, aggregation, and adherence. Of the cytokines examined, TNF-alpha appears to have the greatest direct effects on neutrophil rheology. Similarly, endotoxin appears to have greater direct effects on neutrophil rheology than the Gram-positive bacterial toxins, LTA, and staphylococcal enterotoxins.
Department of Medicine, Saint Vincents Hospital and Medical Center, New York Medical College, NY 10011, USA.
A H
AH
Lavkan
M E
ME
Astiz
E C
EC
Rackow
D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D011446:Prospective Studies; D012212:Rheology / Q000187:drug effects*; D012475:Salmonella; D013210:Staphylococcus; D013682:Teichoic Acids / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004768:Enterotoxins; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid