title: Slp is an essential component of an EDTA-resistant activation pathway of mouse complement.
abstract: Slp (sex-limited protein) is a mouse serum protein encoded by a major histocompatibility complex class III gene. It is considered to be a product of a duplicated complement component C4 gene, but without functional activity. Originally it has been found expressed only in adult males with the S region of the H-2d or H-2s haplotype. In this report we present evidence that Slp is involved in a form of mouse complement activation that occurs after fractionation of serum by polyethylene glycol precipitation. This activation pathway is EDTA-resistant (i.e., independent of classical and alternative pathway activation), is regulated by C1 inhibitor, and leads to the generation of hemolytically active membrane attack complexes. A positive correlation between this EDTA-resistant mouse complement activity and reported Slp levels was found. Direct evidence for a functional role of Slp came from substitution experiments in which purified Slp induced hemolytic activity in polyethylene glycol-fractionated, Slp-deficient mouse serum. Selective depletion of other complement components suggested a role for C1s-, C2, and C5, but not C3, in the Slp-dependent complement activation. A model for this type of mouse complement activation is presented.
authors.affiliation: Eijkman-Winkler Institute for Medical and Clinical Microbiology, Utrecht University, Faculty of Medicine, University Hospital, The Netherlands.
authors.forename: C W
authors.initials: CW
authors.lastname: van den Berg
authors.forename: P
authors.initials: P
authors.lastname: Démant
authors.forename: P C
authors.initials: PC
authors.lastname: Aerts
authors.forename: H
authors.initials: H
authors.lastname: Van Dijk
mesh_terms: D000375:Aging / Q000097:blood*; D000818:Animals; D001798:Blood Proteins / Q000502:physiology*; D003167:Complement Activation / Q000187:drug effects / Q000502:physiology*; D003181:Complement C4 / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology*; D004912:Erythrocytes / Q000276:immunology; D006461:Hemolysis; D006649:Histocompatibility Antigens / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000494:pharmacology; D011817:Rabbits; D013045:Species Specificity
chemical_list: D001798:Blood Proteins; C018386:C4a protein, mouse; D003181:Complement C4; D006649:Histocompatibility Antigens; D011092:Polyethylene Glycols; D004492:Edetic Acid