Properdin plays a protective role in polymicrobial septic peritonitis.
Properdin is a positive regulator of complement activation so far known to be instrumental in the survival of infections with certain serotypes of Neisseria meningitidis. We have generated a fully backcrossed properdin-deficient mouse line by conventional gene-specific targeting. In vitro, properdin-deficient serum is impaired in alternative pathway-dependent generation of complement fragment C3b when activated by Escherichia coli DH5alpha. Properdin-deficient mice and wild-type littermates compare in their levels of C3 and IgM. In an in vivo model of polymicrobial septic peritonitis induced by sublethal cecal ligation and puncture, properdin-deficient mice appear immunocompromised, because they are significantly impaired in their survival compared with wild-type littermates. We further show that properdin localizes to mast cells and that properdin has the ability to directly associate with E. coli DH5alpha. We conclude that properdin plays a significant role in the outcome of polymicrobial sepsis.
Stover
Cordula M
CM
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK. cms13@le.ac.uk
Luckett
Jeni C
JC
Echtenacher
Bernd
B
Dupont
Aline
A
Figgitt
Sue E
SE
Brown
Jane
J
Männel
Daniela N
DN
Schwaeble
Wilhelm J
WJ
D000818:Animals; D002432:Cecum; D003176:Complement C3 / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D048168:Escherichia coli K12 / Q000276:immunology; D005260:Female; D008026:Ligation; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010538:Peritonitis / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D011414:Properdin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011677:Punctures; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*
D003176:Complement C3; D011414:Properdin