The degradation product of the C5a anaphylatoxin C5adesarg retains basophil-activating properties.
The complement cleavage product C5a is a potent agonist of different leukocyte types and also has anaphylatoxic properties through the release of mediators by basophils and tissue mast cells. C5a is very rapidly degraded by serum carboxypeptidase N which cleaves the functionally important carboxy-terminal arginine, generating C5desarg, a chemotactic agonist with little mast cell-activating ability. Here we show that natural human C5adesarg is still a trigger for basophil mediator release superior to other endogenous IgE-independent agonists such as monocyte chemotactic protein (MCP)-1, interleukin (IL)-8, C3a and platelet-activating factor. On a molar basis C5adesarg is only one order of magnitude less potent and about half as efficacious as C5a at inducing basophil degranulation. Priming of basophils with either IL-3, IL-5, granulocyte-macrophage-colony-stimulating factor (GM-CSF) or nerve growth factor (NGF) (with comparable efficacies, but different potencies: IL-3 > NGF > IL-5 > GM-CSF) enhanced histamine release and conditioned the cells to produce large amounts of leukotriene C4 (LTC4), which is not generated by basophils exposed to C5adesarg alone. The efficacy of C5a and C5adesarg at inducing histamine and LTC4 release by primed basophils was similar. Thus, C5adesarg is a stable inducer of release of inflammatory mediators by human basophils, particularly in primed cells, and complement may, therefore, play a role in immediate-type hypersensitivity diseases in allergic late-phase reactions.
Bürgi
B
B
Institut of Clinical Immunology, Inselspital, Bern, Switzerland.
Brunner
T
T
Dahinden
C A
CA
D001491:Basophils / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D015936:Complement C5a / Q000502:physiology; D015937:Complement C5a, des-Arginine / Q000378:metabolism / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology; D006636:Histamine Release; D006801:Humans; D066298:In Vitro Techniques; D017997:Leukotriene C4 / Q000096:biosynthesis; D009504:Neutrophils / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology; D016897:Respiratory Burst
D015937:Complement C5a, des-Arginine; D006133:Growth Substances; D010446:Peptide Fragments; D017997:Leukotriene C4; D015936:Complement C5a