IgE-dependent activation of human lung mast cells is not associated with increased phospholipid methylation.
Enhanced phospholipid methylation has been suggested to be an obligatory process in IgE-dependent stimulus-secretion coupling in human lung mast cells. Our studies with mast cell-enriched lung preparations do not support this hypothesis, demonstrating no increased 3H-methyl radiolabeling of chloroform/methanol-extracted lipids or chromatographically separated phospholipids accompanying anti-IgE-dependent histamine secretion. Inhibitors of transmethylation, 3-deazaadenosine, and homocysteine thiolactone inhibited histamine secretion by both anti-IgE and calcium ionophore A23187, reflecting a requirement of secretion for overall integrity of cellular transmethylation. These agents induced small increases in cAMP concentration which are considered to make at most a minor contribution to this inhibition. The inability of methylation inhibitors to diminish anti-IgE-dependent increases in lung mast cell cAMP levels would suggest that not only does phospholipid methylation have no role in histamine secretion but also it does not participate in the activation of adenylate cyclase by this stimulus.
Benyon
R C
RC
Immunopharmacology Group, University of Southampton, United Kingdom.
Church
M K
MK
Holgate
S T
ST
D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D006636:Histamine Release / Q000187:drug effects; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000502:physiology*; D008168:Lung / Q000166:cytology*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D008745:Methylation; D010743:Phospholipids / Q000378:metabolism*; D014372:Tubercidin / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D010743:Phospholipids; C026408:anti-IgE antibodies; C018258:3-deazaadenosine; D006710:Homocysteine; D007073:Immunoglobulin E; D000001:Calcimycin; C007957:homocysteine thiolactone; D000242:Cyclic AMP; D014372:Tubercidin