title: Architectural remodelling in lungs of rabbits induced by type V collagen immunization: a preliminary morphologic model to study diffuse connective tissue diseases.
abstract: The pathogenesis of diffuse connective tissue diseases (DCTD) is still unknown and has been extensively studied regarding its autoimmunity aspects related to extracellular matrix (ECM) remodelling, with an emphasis on the collagens at the inflammatory site. The present paper describes the pulmonary architectural and repair/remodelling responses to injury after immunization of rabbits with human type V collagen. The animal model consisted of rabbits immunized with collagen mixed with Freund's adjuvant and sacrificed 7, 15, 30, 75, and 120 days after the first of four doses of antigen. Pulmonary architecture remodelling response was evaluated by histology, morphometry, and the immunofluorescence method, according to compartments of reference (parenchyma and interstitium) and injury: 1 inflammation (polymorphonuclear and mononuclear cells); 2-repair (fibrosis) and 3-ECM remodelling (collagen system). The results showed an intense inflammatory involvement of the pulmonary vascular and bronchiolar parenchyma, characterized by increased wall thickness in small arteries, infiltrations by pseudoeosinophils, and mononuclear cells. Progressive remodelling of the pulmonary ECM was characterized by collagen deposition in the septal and bronchovascular interstitium, especially in rabbits sacrifices at 75 and 120 days. The ECM remodelling process was not reproduced when rabbits were inoculated with collagen types I and III. We conclude that the model reproduces morphologic changes similar to those observed in many DCTD, encouraging realization of other experiments to gain a better understanding of the pathogenesis of these diseases.
authors.affiliation: Department of Rheumatology, São Paulo Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Walcy R
authors.initials: WR
authors.lastname: Teodoro
authors.forename: Ana P
authors.initials: AP
authors.lastname: Velosa
authors.forename: Samira S
authors.initials: SS
authors.lastname: Witzel
authors.forename: Ana L
authors.initials: AL
authors.lastname: Garippo
authors.forename: Cecília
authors.initials: C
authors.lastname: Farhat
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Parra
authors.forename: Shigueko
authors.initials: S
authors.lastname: Sonohara
authors.forename: Vera L
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Natalino H
authors.initials: NH
authors.lastname: Yoshinari
mesh_terms: D000818:Animals; D024062:Collagen Type V / Q000276:immunology*; D003240:Connective Tissue Diseases / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D006801:Humans; D007114:Immunization; D008168:Lung / Q000276:immunology / Q000473:pathology*; D011817:Rabbits
chemical_list: D024062:Collagen Type V