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Complement peptides C3a- and C5a-induced mediator release from dissociated human skin mast cells
S G el-Lati1, C A Dahinden, M K Church
1Southampton General Hospital, England, U.K.
The Journal of Investigative Dermatology
|May 1, 1994
Summary
Complement peptides C3a and C5a activate human skin mast cells, releasing histamine but not PGD2. This process is rapid, non-cytotoxic, and calcium-independent, differing from IgE-mediated responses.
Area of Science:
- Immunology
- Cell Biology
- Allergy Research
Background:
- Complement peptides C3a and C5a are known to trigger histamine release from human basophils.
- However, their effect on human lung mast cells is limited, suggesting cell-specific responses.
- Human skin mast cells possess distinct immunocytochemical and functional characteristics compared to lung mast cells.
Purpose of the Study:
- To investigate the capacity of complement peptides C3a and C5a to induce mediator release from human dispersed skin mast cells.
- To compare the potency and efficacy of C3a and C5a in histamine release from skin mast cells versus basophils.
- To elucidate the mechanism of anaphylatoxin-induced mediator release in skin mast cells, including its dependence on calcium and comparison with substance P.
Main Methods:
- Concentration-response and time-course studies were performed on human dispersed skin mast cells.
- Histamine and prostaglandin D2 (PGD2) release were measured following stimulation with C3a and C5a.
- The role of extracellular calcium, peptide catabolism, and specific antagonists were assessed.
- Inhibitors of glycolysis (2-deoxy-D-glucose) and oxidative phosphorylation (antimycin A) were used to evaluate the process's cytotoxicity.
Main Results:
- Both C3a and C5a induced concentration-dependent histamine release from skin mast cells, with C5a being significantly more potent.
- Histamine release was rapid (within 15 seconds), non-cytotoxic, and independent of extracellular calcium.
- The extent of histamine release (15-20%) was lower than that observed in basophils.
- Removal of the C-terminal arginine abolished the activity of C3a and C5a.
- Negligible PGD2 release was observed, suggesting a selective mediator release profile.
- A substance P antagonist did not inhibit C3a- or C5a-induced histamine release, indicating distinct activation pathways.
Conclusions:
- C3a and C5a effectively stimulate human skin mast cells to release histamine through a rapid, non-cytotoxic, and calcium-independent mechanism.
- The activation pathway for C3a and C5a on skin mast cells differs from that of substance P.
- These findings highlight the specific roles of complement anaphylatoxins in mast cell activation and inflammatory responses in the skin.