Fibroblast growth factors mobilize peritoneal macrophage intracellular calcium.
Macrophages have been implicated in the propagation of inflammatory disease. The evidence linking macrophages to inflammation stems from their elicited responses to various extracellular ligands eventually culminating in the elaboration of a variety of inflammatory mediators. As part of an investigation of fibroblast growth factors role in promoting inflammation, we examined one aspect of transmembrane signal transduction, intracellular calcium mobilization following culture of murine peritoneal macrophages with acidic and basic fibroblast growth factor. Peritoneal macrophages displayed a rapid rise in cytosolic calcium from a basal level of 147.6 +/- 25.4 nM to 261.9 +/- 49.9 nM at 3.5 minutes following culture with acidic fibroblast growth. A similar rise in calcium was noted with basic fibroblast growth factor. Titration revealed the maximal effective dose of aFGF and bFGF with respect to calcium response to be 10 ng/ml. Using blockers of both voltage and non-voltage gated channels, the FGF induced rise in cytosolic calcium was specifically abolished. Similarly, using specific 5-lipoxygenase (A69412) or cyclooxygenase (Indomethacin) blockers, the aFGF induced rise in maximal calcium response was reduced by 41% and 96% respectively. On the basis of these data, we speculate on some possible roles that FGF may play in the inflammatory response.
Hackshaw
K V
KV
Dept Internal Medicine, Ohio State University, Columbus, 43210.
Shi
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry; D005346:Fibroblast Growth Factors / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005346:Fibroblast Growth Factors; D002118:Calcium