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Editor,—We approached with enthusiasm the report by Salas and colleagues (
) showing that heparin prevented tumour necrosis factor α induced leucocyte rolling, adhesion, and migration in vivo, as demonstrated using intravital microscopy. The novelty and potential importance of the report were emphasised by the appearance of an accompanying commentary by Perretti and Page (
). Our enthusiasm was tempered, however, by the authors' selective invocation of potential explanations for heparin as an anti-inflammatory agent. While an effect of heparin on the neutrophil integrin adhesion molecule CD11b was described in elegant experiments, heparin almost certainly exerts its anti-inflammatory effects through a range of activities beyond an adhesion molecule target. One of these targets is the superfamily of cytokines known as chemokines, over 40 of which have now been identified.1
Chemokines are small, basic, chemotactic cytokines that mediate leucocyte recruitment to sites of inflammation and immune responses.2 3 In addition, it is now clear that they are crucial to routine immune surveillance and homeostasis.4They have a capacity to bind selectively to a range of glycosaminoglycans, or GAGs, including heparin, in tissues and on the surface of both endothelial cells and leucocytes. This interaction heightens migration along a fixed gradient, or so-called haptotaxis,5 and favours receptor binding.6There is strong evidence that soluble GAGs, including heparin, prevent chemokines binding to their receptors, thus abrogating their chemotactic potential.7
Neither Salas and colleagues nor Perretti and Page chose to mention an anti-chemokine mechanism for the anti-leucocyte migration activity of heparin. We ignore chemokines at our peril though, as their sheer number and abundance, and the intensity of the effort being directed at discovering pharmacological inhibitors of their function, highlight their critical role in inflammation.
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