Low molecular weight heparin inhibits tumor necrosis factor alpha-induced leukocyte rolling.
OBJECTIVE
Heparins may exert several anti-inflammatory actions. This study investigated the impact of low molecular weight heparin (LMWH) on tumor necrosis factor (TNF)-alpha-provoked leukocyte rolling, adhesion and extravascular accumulation.


METHODS
Leukocyte-endothelium interactions and tissue accumulation of leukocytes were induced by TNF-alpha in Balb/c mice and analyzed by the use of intravital microscopy in the mouse cremaster muscle microcirculation.


RESULTS
We observed that administration of 5000 units/kg of LMWH, but not 50 and 500 units/kg, markedly reduced TNF-alpha-induced leukocyte rolling, adhesion and tissue infiltration. Notably, when LMWH was given after TNF-alpha only leukocyte rolling was reduced and no effect was observed on firm adhesion of leukocytes.


CONCLUSIONS
Taken together, these findings indicate that LMWH inhibits TNF-alpha-induced leukocyte accumulation by inhibiting the rolling adhesive interaction which may help explain the anti-inflammatory effects of LMWH.
Wan
M X
MX
Department of Surgery, Malmö University Hospital, Lund University, Sweden.
Zhang
X W
XW
Törkvist
L
L
Thorlacius
H
H
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014409:Tumor Necrosis Factor-alpha