Annals of the American Thoracic Society

The constitutive plasma protein serum amyloid P (SAP, also called PTX2) appears to reduce some of the destructive effects of innate immune cells that contribute to lung injury. In addition to acting as an opsin to promote clearance of debris by macrophages, we and colleagues found that SAP reduces neutrophil adhesion and spreading, inhibits the differentiation of monocytes into fibroblast-like cells called fibrocytes, and promotes the differentiation of both monocytes and macrophages into M2reg regulatory macrophages. A variety of pathways appear to mediate SAP sensing. In a mouse model of acute respiratory distress syndrome, SAP injections block the neutrophil influx into the lungs. With respect to fibrocyte differentiation, SAP appears to override the profibrotic effects of NaCl, hyaluronic acid, and cytokines such as IL-4 and IL-13. In mouse models, SAP injections inhibit cardiac and renal fibrosis. In mouse and rat models of pulmonary fibrosis, SAP injections block fibrosis, and when injections are started when there is fibrosis, SAP reduces the fibrosis. In the murine bleomycin model of lung injury and fibrosis, SAP−/− mice show prolonged inflammation, suggesting that a normal function of SAP is to help resolve inflammation. Patients with pulmonary fibrosis tend to have reduced serum levels of SAP, and in a phase 1b trial on patients with pulmonary fibrosis, a company we costarted (Promedior) found that intravenous SAP tended to improved lung function. Together, these results suggest that a constitutive plasma protein may help to reduce lung injury and fibrosis.

Correspondence and requests for reprints should be addressed to Richard H. Gomer, Ph.D., Texas A&M University, Biology, 301 Old Main Drive, College Station, TX 77845. E-mail:

Author disclosures are available with the text of this abstract at www.atsjournals.org.

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Annals of the American Thoracic Society
12
Supplement 1

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