{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:28:23Z","timestamp":1790692103059,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Factor D (FD) is an essential component of the complement alternative pathway (AP). It is an attractive pharmaceutical target because it is an AP-specific protease circulating in blood. Most components of the complement activation pathways are produced by the liver, but FD is highly expressed by adipose tissue. Two critical questions are: 1) to what degree does adipose tissue contribute to circulating FD levels and 2) what quantity of FD is sufficient to maintain a functional AP? To address these issues, we studied a novel mouse strain with complete lipodystrophy (LD), the fld mouse with partial LD, an FD-deficient mouse, and samples from lipodystrophic patients. FD was undetectable in the serum of LD mice, which also showed minimal AP function. Reconstitution with purified FD, serum mixing experiments, and studies of partial LD mice all demonstrated that a low level of serum FD is sufficient for normal AP activity in the mouse system. This conclusion was further supported by experiments in which wild-type adipose precursors were transplanted into LD mice. Our results indicate that almost all FD in mouse serum is derived from adipose tissue. In contrast, FD levels were reduced \u223c50% in the sera of patients with congenital generalized LD. Our studies further demonstrate that a relatively small amount of serum FD is sufficient to facilitate significant time-dependent AP activity in humans and in mice. Furthermore, this observation highlights the potential importance of obtaining nearly complete inhibition of FD in treating alternative complement activation in various autoimmune and inflammatory human diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1701668","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T16:35:24Z","timestamp":1520872524000},"page":"2786-2797","source":"Crossref","is-referenced-by-count":80,"title":["Contribution of Adipose-Derived Factor D\/Adipsin to Complement Alternative Pathway Activation: Lessons from Lipodystrophy"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6703-2272","authenticated-orcid":false,"given":"Xiaobo","family":"Wu","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Hutson","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonina M","family":"Akk","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita","family":"Mascharak","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at University of California , Los Angeles, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1127-3699","authenticated-orcid":false,"given":"Christine T N","family":"Pham","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Washington University School of Medicine , St. Louis, MO 63110"},{"name":"Section of Rheumatology, Department of Medicine, St. Louis Veterans Affairs Medical Center , St. Louis, MO 63106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis E","family":"Hourcade","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2589-7382","authenticated-orcid":false,"given":"Rebecca","family":"Brown","sequence":"additional","affiliation":[{"name":"Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2514-3441","authenticated-orcid":false,"given":"John P","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1815-5046","authenticated-orcid":false,"given":"Charles A","family":"Harris","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine , St. Louis, MO 63110"},{"name":"Section of Endocrinology, Department of Medicine, St. Louis Veterans Affairs Medical Center , St. Louis, MO 63106"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,4,15]]},"reference":[{"key":"2025030610144070500_r1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1084\/jem.20090633","article-title":"Essential role of mannose-binding lectin-associated serine protease-1 in activation of the complement factor D","volume":"207","author":"Takahashi","year":"2010","journal-title":"J. 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