The effects of heparin and related molecules upon the adhesion of human polymorphonuclear leucocytes to vascular endothelium in vitro

1 The effects of an unfractionated heparin preparation (Multiparin), a low molecular weight heparin preparation (Fragmin) and a selectively O-desulpha ted derivative of heparin lacking anticoagulant activity, have been investi gated for their effects on the adhesion of human polymorphonuclear leucocyt es (PMNs) to cultured human umbilical vein endothelial cells (HECs) in vitr o. The effect of poly-L-glutamic acid, a large, polyanionic molecule was al so studied. 2 Unfractionated heparin (50-1000 U ml(-1)), the O-desulphated derivative ( 0.3-6 mg ml(-1)) and the low molecular weight heparin (50 U-1000 U ml(-1)) all inhibited significantly the adhesion of Cr-51 labelled PMNs to HUVECs s timulated with interleukin-1 beta (IL-1 beta; 10 U ml(-1)), bacterial lipop olysaccharide (LPS; 2.5 mu g ml(-1)) or tumour necrosis factor-alpha (TNF-a lpha; 125 U ml(-1)) for 6 h, whereas poly-L-glutamic acid had no effect. In addition, the three heparin preparations in the same concentration range i nhibited significantly the adhesion of f-met-leu-phe-stimulated PMNs to res ting HUVECs. 3 The effects of unfractionated heparin upon the expression of adhesion mol ecules intercellular adhesion molecule-1 (ICAM-1) and E-selection were also investigated, as were the effects of unfractionated heparin upon adhesion of human PMNs to previously stimulated HUVECs. Heparin had little effect up on levels of expression of these adhesion molecules on stimulated HUVECs. H owever, a profound effect upon PMN adhesion to previously stimulated HUVECs was demonstrated using the same preparation, suggesting that inhibition of adhesion molecule expression is not a major component of the described inh ibitory effects of heparin. 4 Pre-incubation of PMNs with heparin followed by washing inhibited their a dhesion to HUVECs, under different conditions of cellular activation, imply ing that heparin can bind to these cells and exert its anti-adhesive effect s even when not directly present in the system. 5 These observations would suggest that both heparin and a low molecular we ight heparin are capable of inhibiting adhesion of human PMNs to endothelia l cells, an effect not dependent solely upon the polyanionic nature of thes e molecules, nor dependent upon their ability to act as anticoagulants.