{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:27:54Z","timestamp":1774618074693,"version":"3.50.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2000,4,1]],"date-time":"2000-04-01T00:00:00Z","timestamp":954547200000},"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":[[2000,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The role of complement activation in the development of obliterative bronchiolitis, a manifestation of chronic lung allograft rejection, was investigated in the heterotopic rat tracheal allograft model. An increase in intragraft complement components C3 and C5b-9 (membrane attack complex) as well as IgM and IgG deposits were demonstrated during the progressive loss of respiratory epithelium and airway occlusion in nontreated allografts compared with syngeneic grafts. A 7-d treatment with recombinant human soluble complement receptor type 1 (sCR1; 20 mg\/kg\/d, intraperitoneal), an inhibitor of both the classic and alternative complement pathways, significantly decreased epithelial necrosis and intragraft neutrophil infiltration, and reduced obliterative changes by 40%. Immunohistochemical analysis of the grafts showed that sCR1 treatment significantly decreased early C5b-9 and IgG deposits, neutrophil chemoattractant IL-8 immunoreactivity, and ICAM-1 expression. Treatment with sCR1 was associated with increased staining for Th2 cytokines, in particular IL-10, with concomitant downregulation of IL-2 and TNF- \u03b1 immunoreactivity. In contrast, sCR1 treatment did not affect the number of graft-infiltrating CD4+ and CD8+ T cells, CD45+ B cells, ED1+ and ED3+ macrophages, or immune activation with expression of IL-2R \u03b1 or MHC class II. In conclusion, this is the first study to demonstrate that blockade of complement activation attenuates the development of OB and suggests that in addition to T cell-driven responses, humoral and antigen-independent immune responses also operate in the disease process. A blockade of complement activation renders the chemokine milieu unattractive to neutrophils and also modulates the alloimmune response toward Th2 cytokines, which may have an antiproliferative role in fibroproliferative disorders.<\/jats:p>","DOI":"10.1164\/ajrccm.161.4.9901114","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T14:15:01Z","timestamp":1365084901000},"page":"1332-1339","source":"Crossref","is-referenced-by-count":28,"title":["Blockade of Complement Inhibits Obliterative Bronchiolitis in Rat Tracheal Allografts"],"prefix":"10.1093","volume":"161","author":[{"given":"ERKKI A.","family":"KALLIO","sequence":"first","affiliation":[{"name":"Cardiopulmonary Research Group of the Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; and AVANT Immunotherapeutics, Needham, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"KARL B.","family":"LEMSTR\u00d6M","sequence":"additional","affiliation":[{"name":"Cardiopulmonary Research Group of the Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; and AVANT Immunotherapeutics, Needham, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"PEKKA J.","family":"H\u00c4YRY","sequence":"additional","affiliation":[{"name":"Cardiopulmonary Research Group of the Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; and AVANT Immunotherapeutics, Needham, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"UNA S.","family":"RYAN","sequence":"additional","affiliation":[{"name":"Cardiopulmonary Research Group of the Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; and AVANT Immunotherapeutics, Needham, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"PETRI K.","family":"KOSKINEN","sequence":"additional","affiliation":[{"name":"Cardiopulmonary Research Group of the Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; and AVANT Immunotherapeutics, Needham, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,4,1]]},"reference":[{"key":"2026032708425645300_B1","first-page":"691","article-title":"The Registry of the International Society for Heart and Lung Transplantation: Fourteenth Official Report\u20141997.","volume":"16","author":"Hosenpud","year":"1997","journal-title":"J. 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