Low molecular weight heparin inhibits tumor necrosis factor α-induced leukocyte rolling

Abstract.

Objective: Heparins may exert several anti-inflammatory actions. This study investigated the impact of low molecular weight heparin (LMWH) on tumor necrosis factor (TNF)-α-provoked leukocyte rolling, adhesion and extravascular accumulation.¶Materials and methods: Leukocyte-endothelium interactions and tissue accumulation of leukocytes were induced by TNF-α 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-α-induced leukocyte rolling, adhesion and tissue infiltration. Notably, when LMWH was given after TNF-α 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-α-induced leukocyte accumulation by inhibiting the rolling adhesive interaction which may help explain the anti-inflammatory effects of LMWH.