title: Functional relevance of activated beta1 integrins in mercury-induced nephritis.
abstract: Cell adhesion through different adhesion molecules is a crucial event in the inflammatory response. Integrins can only bind and mediate cellular adhesion after their activation by different specific stimuli. The state of beta1 integrin activation can be assessed by a group of monoclonal antibodies (HUTS) that selectively recognize beta1 integrins in their active form. A similar activated epitope in the rat was defined using the anti-human monoclonal antibody HUTS-21, which recognizes an activation-dependent epitope on the beta1 chain. It was found that the divalent cations Mn(2+) and Hg(2+) were able to induce in vitro the activation of beta1 integrins on rat lymphocytes. The Hg(2+) cation induces an autoimmune disease in the Brown Norway rat characterized by synthesis and glomerular deposits of anti-glomerular basement membrane antibodies, proteinuria, and interstitial nephritis. Using the mercury model of nephritis, it was found that the expression of HUTS-21 epitope is induced in vivo in rat lymphocytes, and its appearance is correlated with the other parameters at the onset of the disease. In addition, the administration of HUTS-21 monoclonal antibody to HgCl(2)-treated rats offered evidence of its protective effects (1) against infiltration of renal interstitium by leukocytes, and (2) in the reduction of anti-glomerular basement membrane synthesis and glomerular deposition. Nevertheless, urinary protein values remained unaffected. These results demonstrate a key role of beta1-activated integrins in both leukocyte cell-cell interactions and leukocyte infiltration pathway mechanism, and also indicate that leukocyte migration may have less importance in the development of this disease than previously thought.
authors.affiliation: Department of Pathology, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Escudero
authors.affiliation: Department of Pathology, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Martín
authors.affiliation: Immunology Section, Hospital de la Princesa, Universidad Autónoma, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Nieto
authors.affiliation: Department of Pathology, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Nieto
authors.affiliation: Department of Pathology, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Navarro
authors.affiliation: Department of Biochemistry, Medical School, Universidad Complutense, Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Luque
authors.affiliation: Department of Biochemistry, Medical School, Universidad Complutense, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cabañas
authors.affiliation: Immunology Section, Hospital de la Princesa, Universidad Autónoma, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.affiliation: Department of Pathology, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Mampaso
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002448:Cell Adhesion; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005434:Flow Cytometry; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D008628:Mercury; D009393:Nephritis / Q000139:chemically induced / Q000276:immunology*; D051381:Rats; D011914:Rats, Inbred BN; D016028:Receptors, Leukocyte-Adhesion / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D016028:Receptors, Leukocyte-Adhesion; D008628:Mercury