Substances which aggregate neutrophils. Mechanism of action.
Several agents which influence calcium 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 calcium or phosphate enhanced this effect; 10(-6) M to 10(-5) M lanthanum inhibited it. In addition, the calcium ionophore A23187 aggregated the cells. Aggregation induced by the chemotactic factor and A23187 required extracellular calcium. These results correlate with the known or postulated ability of chemotactic factors, A23187, calcium, phosphate, lanthanum, and cytochalasin B to enhance or inhibit the influx and intracellular accumulation of the calcium ion. Transmembrane fluxes or intracellular levels of calcium may modulate PMN aggregation. Aggregation induced by the chemotactic tripeptide and A23187 also required extracellular magnesium. Since calcium and magnesium 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 magnesium is unknown. Since magnesium, unlike calcium, is known to be necessary for PMN adherence to glass, it may play a permissive role in PMN aggregation. Thus, magnesium 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 calcium or magnesium. This aggregation may result from the formation of intercellular adhesions by the lanthanum ion directly.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology*; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007811:Lanthanum / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D010710:Phosphates / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D010455:Peptides; D010710:Phosphates; D000001:Calcimycin; D003571:Cytochalasin B; D007811:Lanthanum; D009113:Muramidase; D005966:Glucuronidase; D008274:Magnesium; D002118:Calcium