Recombinant soluble human complement receptor type 1 inhibits inflammation in the reversed passive arthus reaction in rats.
The human CR1 was genetically engineered by site directed mutagenesis into a truncated form which was secreted from transfected Chinese hamster ovary cells. This soluble recombinant CR1 (sCR1) was purified from the supernatants of the Chinese hamster ovary cells cultured in a hollow fiber bioreactor. sCR1 inhibits the C3 and C5 convertases of the classical and the alternative pathways in vitro. The ability of sCR1 to inhibit the immune complex-mediated inflammation in vivo was tested in a rat reversed passive Arthus reaction model. Administration of sCR1 at the dermal sites reduced the Arthus vasculitis in a dose-dependent manner as judged by both gross and microscopic examination, as well as by immunohistologic localization of C3 and C5b-9 neoantigen deposits. These data suggest that sCR1 inhibits the Arthus reaction by interrupting the activation of the C cascade, hence limiting the detrimental immune complex-induced tissue damage in vivo.
Yeh
C G
CG
T Cell Sciences, Inc., Cambridge, MA 02139.
Marsh
H C
HC
Carson
G R
GR
Berman
L
L
Concino
M F
MF
Scesney
S M
SM
Kuestner
R E
RE
Skibbens
R
R
Donahue
K A
KA
Ip
S H
SH
D000818:Animals; D001183:Arthus Reaction / Q000276:immunology* / Q000473:pathology; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007116:Immunization, Passive; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D011951:Receptors, Complement / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017463:Receptors, Complement 3b; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification; D012867:Skin / Q000276:immunology / Q000473:pathology; D012995:Solubility; D014162:Transfection
D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011994:Recombinant Proteins; D003165:Complement System Proteins