Peptidergic pathway in human skin and rat peritoneal mast cell activation.
The common pathway of heterogenous mast cell activation as mediated by antigens is through the cross-linking of IgE bound to Fc epsilon RI receptors. The peptidergic pathway of mast cell activation, achieved by cationic secretagogues, is restricted to "serosal" mast cells, the experimental models being rat peritoneal and human skin mast cells. Cationic secretagogues include positively charged peptides but also various amines such as compound 48/80 and natural polyamines. An early intracellular event of this pathway is the activation of pertussis toxin-sensitive G proteins. The correlation observed between the ability of basic compounds to trigger mast cell exocytosis and their potency to activate purified G proteins strongly suggests that cationic compounds activate mast cell G proteins via a receptor-independent but membrane-assisted process. In this paper, alternative mechanisms are discussed. The consequence of G protein stimulation is the activation of phospholipase C with an increase in inositol triphosphates. Natural polyamines are relatively poor triggers of mast cells (10(-4) to 10(-2) M). Neuropeptides such as substance P, neuropeptide Y or vasoactive intestinal peptide, peptidic hormones such as kinins, and venoms such as mastoparan and mast cell degranulating peptide, are all active in a concentration range from 10(-7) to 10(-4) M. The cationic anaphylatoxin C3a also stimulates mast cells at concentrations below precursor complement C3 blood levels. The component C3 of the complement system is one of only a few plasma proteins having activation fragments (i.e. C3a) that can be generated at micromolar levels. The effects of basic secretagogues defines a peptidergic pathway of mast cell activation, which represents a potentially toxic process considering the tissue effects caused by exogenous basic compounds such as venom peptides and certain amine containing drugs. Peptidergic activation of mast cells may also be a pathophysiological process having an important role in neurogenic inflammation and in diseases involving extensive activation of the blood complement cascade.
Mousli
M
M
Laboratoire de Neuroimmunopharmacologie, INSERM CJF-9105, Université Louis Pasteur-Strasbourg I, Illkirch, France.
Hugli
T E
TE
Landry
Y
Y
Bronner
C
C
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000502:physiology*; D010529:Peritoneal Cavity / Q000166:cytology; D011073:Polyamines / Q000494:pharmacology; D051381:Rats; D012867:Skin / Q000166:cytology
D010455:Peptides; D011073:Polyamines; D019204:GTP-Binding Proteins; D002118:Calcium