{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T17:23:21Z","timestamp":1772040201480,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science","award":["18H02649"],"award-info":[{"award-number":["18H02649"]}]},{"name":"Japan Society for the Promotion of Science","award":["20K21516"],"award-info":[{"award-number":["20K21516"]}]},{"name":"Japan Society for the Promotion of Science","award":["21H02722"],"award-info":[{"award-number":["21H02722"]}]},{"name":"Japan Society for the Promotion of Science","award":["22H05057"],"award-info":[{"award-number":["22H05057"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The shedding of cell surface receptors may bring synergistic outcomes through the loss of receptor-mediated cell signaling and competitive binding of the shed soluble receptor to its ligand. Thus, soluble receptors have both biological importance and diagnostic importance as biomarkers in immunological disorders. Signal regulatory protein \u03b1 (SIRP\u03b1), one of the receptors responsible for the \u2018don\u2019t-eat-me\u2019 signal, is expressed by myeloid cells where its expression and function are in part regulated by proteolytic cleavage. However, reports on soluble SIRP\u03b1 as a biomarker are limited. We previously reported that mice with experimental visceral leishmaniasis (VL) manifest anemia and enhanced hemophagocytosis in the spleen accompanied with decreased SIRP\u03b1 expression. Here, we report increased serum levels of soluble SIRP\u03b1 in mice infected with Leishmania donovani, a causative agent of VL. Increased soluble SIRP\u03b1 was also detected in a culture supernatant of macrophages infected with L. donovani in vitro, suggesting the parasite infection promotes ectodomain shedding of SIRP\u03b1 on macrophages. The release of soluble SIRP\u03b1 was partially inhibited by an ADAM proteinase inhibitor in both LPS stimulation and L. donovani infection, suggesting a shared mechanism for cleavage of SIRP\u03b1 in both cases. In addition to the ectodomain shedding of SIRP\u03b1, both LPS stimulation and L. donovani infection induced the loss of the cytoplasmic region of SIRP\u03b1. Although the effects of these proteolytic processes or changes in SIRP\u03b1 still remain unclear, these proteolytic regulations on SIRP\u03b1 during L. donovani infection may explain hemophagocytosis and anemia induced by infection, and serum soluble SIRP\u03b1 may serve as a biomarker for hemophagocytosis and anemia in VL and the other inflammatory disorders.<\/jats:p>","DOI":"10.3390\/pathogens12040593","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T02:03:38Z","timestamp":1681437818000},"page":"593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Leishmania Infection-Induced Proteolytic Processing of SIRP\u03b1 in Macrophages"],"prefix":"10.3390","volume":"12","author":[{"given":"Hana","family":"Hirai","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Hong","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"Fujii","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4581-4038","authenticated-orcid":false,"given":"Chizu","family":"Sanjoba","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8654-7888","authenticated-orcid":false,"given":"Yasuyuki","family":"Goto","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s00436-016-5313-x","article-title":"Prevalence, Severity, and Pathogeneses of Anemia in Visceral Leishmaniasis","volume":"116","author":"Goto","year":"2017","journal-title":"Parasitol. 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