The complement component C3 plays a critical role in both Th1 and Th2 responses to antigen.
BACKGROUND
Complement component C3 is synthesized by keratinocytes and is activated after skin injury. C3 is also synthesized by peritoneal macrophages, which are activated by the adjuvant alum.


OBJECTIVE
We sought to investigate the role of C3 in inciting allergic skin Inflammation and systemic immune responses after epicutaneous sensitization or intraperitoneal sensitization with antigen.


METHODS
C3-deficient (C3-/-) mice and wild-type (WT) control animals were subjected to epicutaneous sensitization with the antigen ovalbumin (OVA) on shaved and tape-stripped skin or intraperitoneal immunization with OVA in alum.


RESULTS
Skin Infiltration by eosinophils and expression of mRNA encoding the TH2 cytokines IL-4 and IL-5 in OVA-sensitized skin sites was impaired in C3-/- mice. Splenocytes from epicutaneously sensitized C3-/- mice secreted less IL-4, IL-5, IL-13, and IFN-gamma in response to OVA stimulation than splenocytes from WT control animals. The defect in cytokine secretion by splenocytes was also observed after intraperitoneal immunization of C3-/- mice. C3-/- mice had impaired IgG1, IgG2a, and IgE antibody responses after both epicutaneous and intraperitoneal immunization. The defect in cytokine secretion of C3-/- mice was not due to defective proliferation to antigen, was not observed after anti-CD3 stimulation, and was corrected by the addition of purified C3 protein.


CONCLUSIONS
These results suggest that C3 plays an important role in both the TH1 and TH2 response to antigen in vivo.


CONCLUSIONS
The complement pathway might be a potential target in the therapy of allergic diseases.
Yalcindag
Ali
A
Division of Immunology, Children's Hospital, Department of Pediatrics, Boston, MA 02115, USA.
He
Rui
R
Laouini
Dhafer
D
Alenius
Harri
H
Carroll
Michael
M
Oettgen
Hans C
HC
Geha
Raif S
RS
D000279:Administration, Cutaneous; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
D000941:Antigens; D003176:Complement C3; D010047:Ovalbumin