Pulmonary expression of the human haptoglobin gene

Haptoglobin (Hp), a member of the acute-phase reactants, has long been know n as a major hemoglobin-binding protein associated with hemoglobin cataboli sm. Recent studies indicate that another important biologic function of Hp is the modulation of the immune response. We found that Hp is expressed at high levels in specific cells, including alveolar macrophages and eosinophi ls in diseased or inflamed human lung tissues, but not in the normal lung. Expression of the human Hp gene was studied in two transgenic mouse lines c arrying a 9-kb human Hp 2 gene. In both lines, the human Hp transgene was e xpressed constitutively in alveolar macrophages at a high level, whereas th e endogenous mouse Hp was synthesized in airway epithelial cells. Expressio n of the human Hp transgene in lung cells was upregulated when the transgen ic mice were treated with endotoxin. In humans and in Hp transgenic mice, h uman Hp messenger RNA was also detected in circulating eosinophils, but not in other blood cells. Our findings suggest that Hp is involved in a variet y of lung inflammatory diseases, including respiratory allergy and asthma. The transgenic mouse line that overexpresses the human Hp gene in alveolar macrophages and eosinophils is a promising system for investigating the fun ction of Hp in vivo during lung inflammation.