SUBSTANCES WHICH AGGREGATE NEUTROPHILS - MECHANISM OF ACTION

Abstract

Several agents which influence Ca fluxes in neutrophils were tested for their influence on human neutrophil aggregation. Formyl-methionyl-leucyl-phenylalanine, a synthetic chemotactic tripeptide, aggregated the cells. Cytochalasin B and high levels of extracellular Ca or phosphate enhanced this effect, and 10-6 M to 10-5 M lanthanum inhibited it. The Ca ionophore A23187 aggregated the cells. Aggregation induced by the chemotactic factor and A23187 required extracellular Ca. These results correlate with the known or postulated ability of chemotactic factors, A23187, Ca, phosphate, lanthanum and cytochalasin B to enhance or inhibit the influx and intracellular accumulation of the Ca2+. Transmembrane fluxes or intracellular levels of Ca may modulate PMN [polymorphonuclear neutrophil] aggregation. Aggregation induced by the chemotactic tripeptide and A23187 also required extracellular Mg. Since Ca and Mg cannot substitute for each other in the aggregation response to the chemotactic factor or A23187, each bivalent cation must play a separate role in PMN aggregation. The role of Mg is unknown. Since Mg, unlike Ca, is known to be necessary for PMN adherence to glass, it may play a permissive role in PMN aggregation. Mg may foster the formation of cell-cell adhesions. In addition to inhibiting chemotactic factor-induced aggregation at concentrations of 10-6 M to 10-5 M, lanthanum, at concentrations of 10-4 M to 10-3 M, aggregated the cells. Lanthanum-induced aggregation did not require extracellular Ca or Mg. This aggregation may result from the formation of intercellular adhesions by the lanthanum ion directly.