title: Selective cleavage of human IgG by the matrix metalloproteinases, matrilysin and stromelysin.
abstract: We have shown that two of the matrix metalloproteinases (MMPs), matrilysin and stromelysin-1, are capable of cleaving all of the human IgG subclasses. The cleavage occurs at a conserved site in the CH(2) domain of the heavy chain of IgG, releasing a single chain Fc-like fragment. We have not been able to demonstrate cleavage of IgA, IgD, IgM or IgE classes, which lack the cleavage site, nor could we show cleavage of IgG by collagenase, gelatinase, macrophage metalloelastase or membrane-type (MT)-MMP. This cleavage of IgG, by separating the antigen-binding (Fabprime prime or minute)(2) from the Fc portion, will remove much of the immunoglobulins' functionality, e.g. complement fixation, Fc receptor binding. In the context of a tumour producing matrilysin or stromelysin, this may represent a way in which the tumour protects itself from ADCC. In inflamed or damaged tissues where plasma protein leakage occurs, degradation by MMPs may be a mechanism for clearance of IgG.
authors.affiliation: British Biotech Pharmaceuticals Ltd., Oxford OX4 5LY, UK.
authors.forename: Andrew J H
authors.initials: AJ
authors.lastname: Gearing
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Thorpe
authors.forename: Karen
authors.initials: K
authors.lastname: Miller
authors.forename: Matthew
authors.initials: M
authors.lastname: Mangan
authors.forename: Paul G
authors.initials: PG
authors.lastname: Varley
authors.forename: Tim
authors.initials: T
authors.lastname: Dudgeon
authors.forename: George
authors.initials: G
authors.lastname: Ward
authors.forename: Christina
authors.initials: C
authors.lastname: Turner
authors.forename: Robin
authors.initials: R
authors.lastname: Thorpe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008969:Molecular Sequence Data; D010206:Papain / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D007074:Immunoglobulin G; D011994:Recombinant Proteins; D010206:Papain; D010434:Pepsin A; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7