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* Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005; and
Department of Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030
Fibrotic diseases such as scleroderma, severe chronic asthma, pulmonary fibrosis, and cardiac fibrosis kill tens of thousands of people each year in the U.S. alone. Growing evidence suggests that in fibrotic lesions, a subset of blood monocytes enters the tissue and differentiates into fibroblast-like cells called fibrocytes, causing tissue dysfunction. We previously found that a plasma protein called serum amyloid P (SAP) inhibits fibrocyte differentiation in vitro. Bleomycin treatment is a standard model for pulmonary fibrosis, and causes an increase in collagen, fibrocytes, and leukocytes in the lungs, and a decrease in peripheral blood hemoglobin oxygen saturation. We find that injections of rat SAP in rats reduce all of the above bleomycin-induced changes, suggesting that the SAP injections reduced the bleomycin-induced pulmonary fibrosis. We repeated these studies in mice, and find that injections of murine SAP decrease bleomycin-induced pulmonary fibrosis. To confirm the efficacy of SAP treatment, we used a delayed treatment protocol using SAP from day 7 to 13 only, and then measured fibrosis at day 21. Delayed SAP injections also reduce the bleomycin-induced decrease in peripheral blood hemoglobin oxygen saturation, and an increase in lung collagen, leukocyte infiltration, and fibrosis. Our data suggest the possibility that SAP may be useful as a therapy for pulmonary fibrosis in humans.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Howard Hughes Medical Institute, Grant 005/04 from the Scleroderma Foundation, Grant C-1555 from the Robert A. Welch Foundation, and National Institutes of Health Grants CA64193 and HL083029.
2 Address correspondence and reprint requests to Dr. Darrell Pilling, Department of Biochemistry and Cell Biology, MS-140, Rice University, Houston, TX 77005-1894. E-mail address: dpilling{at}rice.edu
3 Abbreviations used in this paper: SAP, serum amyloid P; 
-SMA, -smooth muscle actin; CRP, C-reactive protein; DAPI, 4',6'-diamidino-2-phenylindole; pulse Ox, percentage of hemoglobin saturated with oxygen.
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