Reduction of bleomycin-induced pulmonary fibrosis by serum amyloid P.
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.
Pilling
Darrell
D
Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA. dpilling@rice.edu
Roife
David
D
Wang
Min
M
Ronkainen
Sanna D
SD
Crawford
Jeff R
JR
Travis
Elizabeth L
EL
Gomer
Richard H
RH
D000818:Animals; D001761:Bleomycin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002452:Cell Count; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007274:Injections, Intraperitoneal; D007442:Intubation, Intratracheal; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000683:Serum Amyloid P-Component / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors