Rapid intracellular calcium changes in U937 monocyte cell line: transient increases in response to platelet-activating factor and chemotactic peptide but not interferon-gamma or lipopolysaccharide.
The dye fura-2, a potentially more sensitive successor to quin2 for measuring intracellular free calcium ion concentrations [(Ca2+]i), has been applied here to investigate the possible involvement of early changes in [Ca2+]i in the stimulation of the human monocyte-macrophage-like cell line U937. The calcium ionophores A23187 and ionomycin, known pharmacological stimuli for macrophages, were found to cause sharp rises in [Ca2+]i as expected. Responses analogous to those reported for a murine macrophage cell (J774) were obtained on stimulation of U937 cells with ATP which caused rapid, but transient, increases in [Ca2+]i (from resting levels of about 70 nM to peaks of about 200 mM). In addition to ATP, several agents known to activate macrophages were used as stimuli. In particular, platelet-activating factor (PAF; 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) was found to cause rapid, but transient, increases in [Ca2+]i (from resting levels of about 70 nM to peaks of about 400 nM) even at concentrations as low as 10(-10) M. This contrasts with responses to ATP that were markedly reduced at 10(-6) M compared with 10(-5) M or above, suggesting that PAF is a highly potent stimulus for intracellular calcium mobilization in macrophages. Similar responses were obtained with chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine). On the other hand, two agents known to be potent activators of macrophages, interferon gamma and lipopolysaccharide, had no rapid effect on [Ca2+]i. This may reflect differences in the kinetics of signal-response coupling or alternatively a different mechanism of action by-passing the need for rapid elevation of [Ca2+]i.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*
D007476:Ionophores; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007371:Interferon-gamma; D000255:Adenosine Triphosphate; D002118:Calcium