Synergistic effect of heparin and chemotactic factor on polymorphonuclear leukocyte aggregation and degranulation

The in vitro effects of therapeutic amounts of polyanionic heparin on human polymorphonuclear leukocytes (PMN) aggregation and on the release of cationic lactoferrin from PMN-specific granules were investigated. Incubation of 1 X 10(7) human PMNs with 0.3 unit/ml of heparin followed by stimulation with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) 2 X 10(-7) M significantly increased PMN aggregation, compared with controls. Cytochalasin B potentiated aggregation, which was further increased by incubation of the PMNs with heparin. Similarly, heparin also increased PMN degranulation and lactoferrin release following stimulation with FMLP with or without cytochalasin B, compared with controls. In addition, human lactoferrin complexed with heparin on a sucrose density gradient and caused a significant shift in the migration of 3H-heparin. Finally, rabbits pretreated with intravenous heparin resulting in prolongation of their activated partial thromboplastin time (APTT) to 1.5 to 2.5 times baseline had more profound reduction in PMN counts following a challenge with the secretagogue phorbol myristate acetate (PMA). These studies demonstrate that heparin can interact synergistically with chemotactic stimuli known to evoke lactoferrin release, which in turn leads to enhancement of PMN aggregation. Our data further suggest that heparin may be contraindicated in the treatment of syndromes with increased PMN aggregation such as endotoxin-induced Schwartzman-type reactions.