Aggregation of human neutrophils by heparin

Commercial heparin preparations induce the aggregation of human polymorphonuclear neutrophils (PMNs). The minimum aggregating concentration (MAC) of different heparin lots was measured under standardized conditions. It was found to vary between 0.3 and 15 units/ml. Gel filtration of heparin showed that the aggregating activity eluted in a sharp peak with a pattern different from heparin. When heparin was bound to antithrombin III-Sepharose, the aggregating activity eluted totally in the high-affinity fraction. When PMNs are partially aggregated with heparin, further aggregation by N-formyl-methionyl-leucyl-phenylalanine (FMLP) or phorbol myristate-acetate (PMA) is not affected. Pretreatment of PMNs with a low-aggregating heparin fraction, inhibits further aggregation by a high-aggregating heparin fraction. These results suggest that the PMNs have binding sites for heparin different from those for PMA and FMLP. Binding of heparin is not enough for inducing aggregation. Certain structural requirements of the heparin molecule are probably essential for aggregation.