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T_H2-Mediated Pulmonary Inflammation Leads to the Differential Expression of Ribonuclease Genes by Alveolar Macrophages

Divisions of Hematology/Oncology and Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, S.C. Johnson Medical Research Center, Scottsdale, Arizona

Address correspondence to: Dr. James (Jamie) J. Lee, Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, 13400 East Shea Boulevard, Scottsdale, AZ 85259. E-mail: jlee{at}mayo.edu

The eosinophil-associated ribonuclease (Ear) family in the mouse consists of thirteen genes, eleven of which encode RNases that have physical/functional properties similar to the human Ears, eosinophil-derived neurotoxin and eosinophil cationic protein. The expression of Ear genes in the mouse is confined to sites of known eosinophilopoiesis, with the exception of the lung. Two Ear genes, Ear1 and Ear2, are predominantly expressed in the lungs of naive mice. Total Ear gene expression and RNase activity in bronchoalveolar lavage fluid increases significantly upon the induction of pulmonary inflammation using an ovalbumin (OVA) model of allergic sensitization and challenge. Interestingly, pulmonary Ear11 transcripts, which are absent in naive mice, accumulate as a consequence of OVA-mediated T_H2 inflammation in the lung. The induction of Ear11 expression is dependent on the presence of T cells, in particular, CD4⁺ T lymphocytes. This effect is likely the result of the elaboration of T_H2 cytokine levels, because pulmonary instillation of interleukin-4 or interleukin-13 induces the accumulation of Ear11 transcripts in naive animals. This study demonstrates that despite an allergen-mediated pulmonary eosinophilia and earlier studies showing that Ears are constituents of eosinophil secondary granules, alveolar macrophages are a significant source of these RNases in lungs of OVA-treated mice.

Abbreviations: bronchoalveolar lavage, BAL • BAL fluid, BALF • eosinophil-associated ribonuclease, Ear • eosinophil cationic protein, ECP • eosinophil-derived neurotoxin, EDN • glyceraldehyde 3-phosphate dehydrogenase, GAPDH • major basic protein, MBP • ovalbumin, OVA • respiratory syncytial virus, RSV • ribonuclease, RNase • saline, SAL

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