Relationships between phosphoinositide metabolism, Ca2+ changes and respiratory burst in formyl‐methionyl‐leucyl‐ phenylalanine‐stimulated human neutrophils

Abstract

The relationships between the changes of cellular Ca²⁺ the activation of phosphoinositide turnover and the functional responses induced by the stimulus-receptor interactions in neutrophils are matter of controversy. By measuring the concentration dependency of different formyl-leucyl-methionyl-phenylalanine (FMLP)-induced changes, the following values of ED₅₀ were found: 1.6 and 0.8 nM for the rise in [Ca²⁺]_i monitored with Quin-2, in the presence and absence of exogenous Ca²⁺ respectively; 20 nM for the activation of phosphoinositide metabolism, monitored as change in the ³²P_i of phosphatidate; 14 nM for membrane-bound Ca²⁺ mobilization, monitored with chlorotetracycline (CTC); 34 nM for ⁴⁵Ca²⁺ influx and 32 nM for the respiratory burst. Furthermore, low dose of FMLP causes an increase in [Ca²⁺]_i in absence of activation of breakdown of phosphatidylinositol, phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-biphosphate monitored as changes in [³H]glycerol radioactivity. The results clearly demonstrate that the increase in [Ca²⁺]_i, due to the release from intracellular stores, is not caused by the breakdown of phosphatidylinositides. On the other hand, the data of the similarity of ED₅₀ are compatible with an involvement of phosphoinositide response in the release of membrane bound Ca²⁺, monitored with CTC, and in the ⁴⁵Ca influx and in the respiratory burst.