Persistent lung inflammation and fibrosis in serum amyloid P component (APCs-/-) knockout mice.
Fibrosing diseases, such as pulmonary fibrosis, cardiac fibrosis, myelofibrosis, liver fibrosis, and renal fibrosis are chronic and debilitating conditions and are an increasing burden for the healthcare system. Fibrosis involves the accumulation and differentiation of many immune cells, including macrophages and fibroblast-like cells called fibrocytes. The plasma protein serum amyloid P component (SAP; also known as pentraxin-2, PTX2) inhibits fibrocyte differentiation in vitro, and injections of SAP inhibit fibrosis in vivo. SAP also promotes the formation of immuno-regulatory Mreg macrophages. To elucidate the endogenous function of SAP, we used bleomycin aspiration to induce pulmonary inflammation and fibrosis in mice lacking SAP. Compared to wildtype C57BL/6 mice, we find that in Apcs-/- "SAP knock-out" mice, bleomycin induces a more persistent inflammatory response and increased fibrosis. In both C57BL/6 and Apcs-/- mice, injections of exogenous SAP reduce the accumulation of inflammatory macrophages and prevent fibrosis. The types of inflammatory cells present in the lungs following bleomycin-aspiration appear similar between C57BL/6 and Apcs-/- mice, suggesting that the initial immune response is normal in the Apcs-/- mice, and that a key endogenous function of SAP is to promote the resolution of inflammation and fibrosis.
Department of Biology, Texas A&M University, College Station, Texas, United States of America.
Darrell
D
Pilling
Department of Biology, Texas A&M University, College Station, Texas, United States of America.
Richard H
RH
Gomer
D000818:Animals; D001761:Bleomycin; D002454:Cell Differentiation; D008168:Lung / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000235:genetics* / Q000473:pathology; D000683:Serum Amyloid P-Component / Q000235:genetics*
D000683:Serum Amyloid P-Component; D001761:Bleomycin