title: Cleavage of immunoglobulin G (IgG) and IgA around the hinge region by proteases from Serratia marcescens.
abstract: Seven clinical and two nonclinical isolates of Serratia marcescens were examined for their ability to produce extracellular enzymes that cleave immunoglobulin G (IgG) and IgA molecules. All seven clinical isolates excreted a large amount of a 56-kilodalton (kDa) protease (56K protease) and small amounts of a 60-kDa and a 73-kDa protease (60K and 73K proteases, respectively) in culture medium during growth. All purified proteases cleaved IgG and IgA effectively if the level of protease production exceeded 2 to 5 micrograms/ml. The proteolytic activity in the culture supernatant was inhibited by about 85% by a chelating agent (EDTA), which indicated that the major immunoglobulin-cleaving enzyme is the metalloprotease(s) reported previously. Immunological quantification of proteases by single radial immunodiffusion showed similar results: the amount of 56K protease was about 65% and those of the 60K and 73K proteases were about 20 and 5%, respectively. Incubation for 3 h at 37 degrees C was required to generate immunoreactive Fab and Fc fragments. Further analysis of the cleavage products of IgG or IgA demonstrated that the 56K protease, as well as the 60K and 73K proteases, cleaves only the heavy chain of these immunoglobulins near the hinge region to generate Fab and Fc fragments. The susceptibilities of the subclasses of IgG and IgA to the 56K protease were as follows: IgG3 greater than IgG1 greater than IgG2 greater than IgG4 and IgA1 greater than IgA2. IgG2, IgG4, and IgA2 were relatively resistant to the 56K protease.
mesh_terms: D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007128:Immunoglobulin Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism*; D007132:Immunoglobulin Isotypes / Q000378:metabolism; D007137:Immunoglobulin alpha-Chains / Q000378:metabolism; D007142:Immunoglobulin gamma-Chains / Q000378:metabolism; D008970:Molecular Weight; D010447:Peptide Hydrolases / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D012706:Serratia marcescens / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D007070:Immunoglobulin A; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007137:Immunoglobulin alpha-Chains; D007142:Immunoglobulin gamma-Chains; D011480:Protease Inhibitors; D010447:Peptide Hydrolases