Microarray analysis of a mouse model of transfusion‐related acute lung injury (TRALI) reveals prominent increased expression of neutrophil‐derived chemokines
2007; Wiley; Volume: 21; Issue: 6 Linguagem: Inglês
10.1096/fasebj.21.6.a1202-c
ISSN1530-6860
AutoresMark R. Looney, Rebecca Barbeau, Andrea J. Barczak, Yuanyuan Xiao, Clifford A. Lowell, David J. Erle, Michael A. Matthay,
Tópico(s)S100 Proteins and Annexins
ResumoOBJECTIVE: We have reported in a mouse model of transfusion-related acute lung injury (TRALI) that the mechanism of lung injury is dependent on the neutrophil. We have now analyzed the whole lung response in this model using a DNA microarray approach. METHODS: BALB/c mice were challenged with either MHC I mAb (n=3) or isotype control mAb (n=3). The lungs were removed after two hours. RNA was isolated and transcript expression in TRALI and control animals was compared using MEEBO arrays, which include probes for nearly all known mouse genes. Selected ELISA assays were also done using mouse plasma. RESULTS: Microarray analysis revealed 310 transcripts that were increased or decreased by at least 2-fold in TRALI and reached statistical significance (log-odds ratio > 0). Many of the most highly induced transcripts encode neutrophil-derived chemokines (Table). Gene products chemotactic for neutrophils (CXCL1, CXCL2, Calgranulin A & B, CCL3, CXCR2) and other cell types were identified. DCIP-1 is a novel neutrophil chemokine produced by dendritic cells that has not previously been associated with lung injury. Plasma levels of several of the highest differentially expressed genes were also elevated (Table, mean ± sd, ∗p<0.01 TRALI vs. control). CONCLUSIONS: A mouse model of TRALI is characterized by robust increases in neutrophil-derived chemokine mRNA transcripts and proteins in the lung. Supported by NIH HL072301 and HL081027
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