Comparative analysis of the pathological events involved in immune and non-immune TRALI models

Author(s)

Tamarozzi, M. B. ^{[1, 2]} ; Soares, S. G. ^[3] ; Sa-Nunes, A. ^[4] ; Paiva, H. H. ^{[1, 2]} ; Saggioro, F. P. ^[5] ; Garcia, A. B. ^{[1, 2]} ; Lucena-Araujo, A. R. ^{[1, 2]} ; Falcao, R. P. ^{[1, 2]} ; Bordin, J. O. ^[6] ; Rego, E. M. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Internal Med, Div Hematol Oncol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Natl Inst Sci & Technol Stem Cell & Cell Therapy, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Invent Biotecnol, Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Expt Immunol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Pathol, BR-14049900 Ribeirao Preto, SP - Brazil

^[6] Univ Fed Sao Paulo, Hematol & Hemotherapy Div, Sao Paulo - Brazil

• Document type: Journal article
• Source: Vox Sanguinis; v. 103, n. 4, p. 309-321, NOV 2012.
• Web of Science Citations: 4

Abstract

Background and Objectives Transfusion-related acute lung injury (TRALI) is characterized by leukocyte transmigration and alveolar capillary leakage shortly after transfusion. TRALI pathogenesis has not been fully elucidated. In some cases, the infusion of alloantibodies (immune model), whereas in others the combination of neutrophil priming by proinflammatory molecules with the subsequent infusion of biological response modifiers (BRMs) in the hemocomponent (non-immune model) have been implicated. Our aim was to compare the pathological events involved in TRALI induced by antibodies or BRMs using murine models. Materials and Methods In the immune model, human HNA-2+ neutrophils were incubated in vitro with a monoclonal antibody (anti-CD177, clone 7D8) directed against the HNA-2 antigen and injected i.v. in NOD/SCID mice. In the non-immune model, BALB/c mice were treated with low doses of lipopolysaccharide (LPS) followed by platelet-activating factor (PAF) infusion 2 h later. Forty minutes after PAF administration, or 6 h after neutrophil injection, lungs were isolated and histological analysis, determination of a variety of cytokines and chemokines including keratinocyte-derived chemokine (KC), MIP-2, the interleukins IL-1 beta, IL-6, IL-8 as well as TNFa, cell influx and alveolar capillary leakage were performed. Results In both models, characteristic histological findings of TRALI and an increase in KC and MIP-2 levels were detected. In contrast to the immune model, in the non-immune model, there was a dramatic increase in IL-1 beta and TNFa. However, capillary leakage was only detected if PAF was administrated. Conclusions Regardless of the triggering event(s), KC, MIP-2 and integrins participate in TRALI pathogenesis, whereas PAF is essential for capillary leakage when two events are involved. (AU)

• FAPESP's process: 98/14247-6 - Center for Research on Cell-Based Therapy
• Grantee: Marco Antonio Zago
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC