title: Comparative cell signalling activity of ultrapure recombinant chaperonin 60 proteins from prokaryotes and eukaryotes.
abstract: Heat-shock protein (hsp)60/chaperonin 60 is a potent immunogen which has recently been claimed to have cell-signalling actions upon myeloid and vascular endothelial cells. The literature is controversial with different chaperonin 60 proteins producing different patterns of cellular activation and the ever-present criticism that activity is the result of bacterial contaminants. To clarify the situation we have cloned, expressed and purified to homogeneity the chaperonin 60 proteins from Chlamydia pneumoniae, Helicobacter pylori and the human mitochondrion. These highly purified proteins were compared for their ability to stimulate human peripheral blood mononuclear cell (PBMC) cytokine synthesis and vascular endothelial cell adhesion protein expression. In spite of their significant sequence homology, the H. pylori protein was the most potent PBMC activator with the human protein the least potent. PBMC activation by C. pneumoniae and human, but not H. pylori, chaperonin 60 was blocked by antibody neutralization of Toll-like receptor-4. The C. pneumoniae chaperonin 60 was the most potent endothelial cell activator, with the human protein being significantly less active than bacterial chaperonin 60 proteins. These results have implications for the role of chaperonin 60 proteins as pathological factors in autoimmune and cardiovascular disease, and raise the possibility that each of these proteins may result in different pathological effects in such diseases.
authors.affiliation: Division of Microbial Diseases, Eastman Dental Institute, University College London, London, UK. maria_maguire2002@yahoo.co.uk
authors.forename: Maria
authors.initials: M
authors.lastname: Maguire
authors.forename: Stephen
authors.initials: S
authors.lastname: Poole
authors.forename: Anthony R M
authors.initials: AR
authors.lastname: Coates
authors.forename: Peter
authors.initials: P
authors.lastname: Tormay
authors.forename: Caroline
authors.initials: C
authors.lastname: Wheeler-Jones
authors.forename: Brian
authors.initials: B
authors.lastname: Henderson
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000276:immunology* / Q000302:isolation & purification; D016993:Chlamydophila pneumoniae / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism; D005057:Eukaryotic Cells / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D008928:Mitochondria / Q000276:immunology; D011387:Prokaryotic Cells / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013045:Species Specificity; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D015815:Cell Adhesion Molecules; D018834:Chaperonin 60; D016207:Cytokines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors