Studies on pharmacological activation of human serum immunoglobulin G by chemical modification and active subfragments. IV. Induction of anti-inflammatory activity by chemical cleavage of interchain disulfide bonds in human immunoglobulin G and pharmacological activity of alkylated subfragments.
Commercially available human serum immunoglobulin G (IgG, native IgG) was separated into two fractions (Fr.I and II) using a diethylaminoethyl cellulose column. Heavy and light chains containing fractions were obtained from these two fractions after carboxamide-methylation. Thus, these fractions were subjected to an anti-inflammatory screening procedure and were shown to have a potent inhibitory activity against rat carrageenin induced paw edema, while no effect was observed in native IgG, Fr.I or II. The reduction and alkylation of the interchain disulfide bonds were essential to induce the anti-inflammatory activity. The anti-inflammatory activity of alkylated heavy and light chains of Fr.I (Fr.I-H and I-L) was also noted in subacute inflammation caused by the felt pellet and croton oil granuloma methods. Moreover, strong membrane stabilizing activities of Fr.I-H and I-L were demonstrated in vitro using rat red blood cell membrane and liver lysosomal membrane.
T
T
Mimura
K
K
Tsujikawa
H
H
Nakajima
M
M
Okabe
Y
Y
Kohama
M
M
Iwai
K
K
Yokoyama
D000478:Alkylation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D002850:Chromatography, Gel; D003907:Dexamethasone / Q000494:pharmacology; D004220:Disulfides / Q000032:analysis; D004487:Edema / Q000209:etiology / Q000517:prevention & control; D004910:Erythrocyte Membrane / Q000187:drug effects; D006099:Granuloma / Q000378:metabolism; D007128:Immunoglobulin Fragments / Q000032:analysis; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000032:analysis; D066298:In Vitro Techniques; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D004220:Disulfides; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D003907:Dexamethasone