Abstract
It has been shown that heparin can exhibit anti-inflammatory activity independent of its anti-coagulant activity. However, little is known about the precise mechanisms underlying this anti-inflammatory activity. We have therefore investigated the activity of some heparin related compounds on rolling, adhesion and diapedesis of leukocytes in the airways. Methods: N-Acetyl-de-O-Sulphated Heparin (NSH) (20mg/kg) was given orally 30 min prior 10 µg/mice of intranasal instillation or subcutaneous injection of bacterial lipopolysaccharide (LPS) in Balb/c mice. Animals were prepared for intravital microscopy of the trachea 4h later. Results: Mice exhibited higher numbesr of cells rolling (cells x 100µm2) along the vessel wall in 30 sec in response to LPS in the cremaster muscle and tracheal tissue (sal:0.5 ± 0.2 vs LPS: 3.4±0.4; sal:2.5±0.3 vs LPS 15.3± 2.4, respectively; n =5, p < 0.05). LPS also induced a significant increase in the number of adherent cells to the vessel wall in both tissues (sal:0.2 ± 0.2 vs LPS: 12.4±2.4; sal:0.5±0.3 vs LPS 12.3± 1.4, cremaster muscle and trachea, respectively; n =5, p < 0.05). Pre-treatment with NSH significantly inhibited rolling of cells in the tracheal tissue, but not in the cremaster muscle (LPS/NSH: 6.2 ± 1.9, n=5; p < 0.05 vs LPS alone). Conversely, pre-treatment with NSH significantly altered adhesion of leukocytes to the vessel wall in the cremaster muscle, but not in the tracheal tissue (LPS/NSH: 4.2 ± 0.2, n=5; p < 0.05 vs LPS alone). Conclusion: The effect of NSH on leukocyte diapedesis is tissue dependent and confirms the ability of heparin like molecules lacking anti-coagulant activity having anti-inflammatory activity.
- © 2013 ERS
