Ca2+ signalling delays in neutrophils: effects of prior exposure to platelet activating factor or formyl-met-leu-phe.
Rapid-time confocal scanning of fluo3-loaded neutrophils revealed that in individual cells there were grossly heterogeneous time intervals between stimulation with either f-met-leu-phe or platelet activating factor (PAF) and the initiation of Ca2+ influx, ranging from 75 msec to several seconds. The distribution of lag times after stimulation with f-met-leu-phe (100 nM) was influenced by prior stimulation with either f-met-leu-phe or PAF. However, whereas prior stimulation with f-met-leu-phe (50 nM) caused the subsequent cytosolic free Ca2+ response to second challenge with f-met-leu-phe to be delayed, prior stimulation with PAF (100 nM) caused an increase in the rapidity of the onset of the second response to f-met-leu-phe. With both stimuli, the cytosolic free Ca2+ in some neutrophils (non-Ca2+ responders) in the population did not increase significantly. However, some of these cells responded to the subsequent challenge. However, with both pre-treatment stimuli, those cells in which a significant Ca2+ response was provoked by the first stimulus, responded significantly faster than the initial 'non-Ca2+ responders.' However, the reduced lag time provoked by pre-stimulation was not inhibited in neutrophils in which cytosolic free Ca2+ changes were dampened by intracellular BAPTA. These data point to post-receptor events, other than prior cytosolic free Ca2+ elevation, being important in determining the response Ca2+ delay to subsequent stimulation.
Pettit
E J
EJ
Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Hallett
M B
MB
D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology*; D015398:Signal Transduction; D013997:Time Factors
D010972:Platelet Activating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium