{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T12:54:04Z","timestamp":1762520044962,"version":"3.37.3"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2008,8,14]],"date-time":"2008-08-14T00:00:00Z","timestamp":1218672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001862","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["06X-12634","06XD-14653"],"award-info":[{"award-number":["06X-12634","06XD-14653"]}],"id":[{"id":"10.13039\/501100001862","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003748","name":"Swedish Society for Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003748","id-type":"DOI","asserted-by":"publisher"}]},{"name":"King Oscar II Jubilee Foundation"},{"name":"Magnus Bergwall Foundation"},{"DOI":"10.13039\/501100007687","name":"Swedish Medical Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007435","name":"\u00c5ke Wiberg foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007435","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006313","name":"Swedish Childhood Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006313","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The innate immune system produces a number of effector molecules that are important for protection against bacterial infections. Neutrophils and antimicrobial peptides are major components of innate defense with the capacity of rapid bacterial killing. Patients with severe congenital neutropenia (SCN) experience recurrent and chronic infections despite recombinant G-CSF-mobilized neutrophils. We have shown previously that these neutrophils are deficient in that they lack the antimicrobial peptide LL-37. Here, we show that pro-LL-37 mRNA is not expressed in neutrophil precursors from patients with SCN, although the gene and promoter region for pro-LL-37, CAMP, does not display any mutations. The hormonal form of vitamin D3 [1,25(OH)2D3] induced the expression of pro-LL-37 in isolated neutrophil progenitors and in EBV-transformed B cells from patients with SCN, whereas all-trans retinoic acid only induced expression in transformed B cells. These results demonstrate that myeloid cells of patients with SCN can produce pro-LL-37, suggesting that other pathways are impaired.<\/jats:p>","DOI":"10.1189\/jlb.0607437","type":"journal-article","created":{"date-parts":[[2008,8,15]],"date-time":"2008-08-15T01:29:26Z","timestamp":1218763766000},"page":"1279-1286","source":"Crossref","is-referenced-by-count":23,"title":["Vitamin D3 induces pro-LL-37 expression in myeloid precursors from patients with severe congenital neutropenia"],"prefix":"10.1093","volume":"84","author":[{"given":"Jenny","family":"Karlsson","sequence":"first","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm , Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00f6ran","family":"Carlsson","sequence":"additional","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital Solna , Stockholm , Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"Larne","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm , Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mats","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm , Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"P\u00fctsep","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm , Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,8,14]]},"reference":[{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1651-2227.1956.tb06875.x","article-title":"Infantile genetic agranulocytosis; agranulocytosis infantalis hereditaria","volume":"45","author":"Kostmann","year":"1956","journal-title":"Acta Paediatr."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/ajh.10255","article-title":"Severe chronic neutropenia: treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry","volume":"72","author":"Dale","year":"2003","journal-title":"Am. J. Hematol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1182\/blood.V96.7.2317","article-title":"Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia","volume":"96","author":"Dale","year":"2000","journal-title":"Blood"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/ng1940","article-title":"HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)","volume":"39","author":"Klein","year":"2007","journal-title":"Nat. Genet."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/j.1365-2141.2007.06530.x","article-title":"Low plasma levels of the protein pro-LL-37 as an early indication of severe disease in patients with chronic neutropenia","volume":"137","author":"Karlsson","year":"2007","journal-title":"Br. J. Haematol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"99","DOI":"10.17796\/jcpd.26.1.n1vhq267271378l1","article-title":"Oral manifestations of congenital neutropenia or Kostmann syndrome","volume":"26","author":"Defraia","year":"2001","journal-title":"J. Clin. Pediatr. Dent."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1902\/jop.2006.050191","article-title":"Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia","volume":"77","author":"Carlsson","year":"2006","journal-title":"J. Periodontol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1080\/080352501750315663","article-title":"Infantile genetic agranulocytosis, morbus Kostmann: presentation of six cases from the original \u201cKostmann family\u201d and a review","volume":"90","author":"Carlsson","year":"2001","journal-title":"Acta Paediatr."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/S0140-6736(02)11201-3","article-title":"Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study","volume":"360","author":"Putsep","year":"2002","journal-title":"Lancet"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"2772","DOI":"10.1182\/blood-2007-03-083063","article-title":"Expression of granule-associated proteins in neutrophils from patients with severe congenital neutropenia","volume":"110","author":"Andersson","year":"2007","journal-title":"Blood"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1034\/j.1600-065X.2000.917301.x","article-title":"Innate immunity and the normal microflora","volume":"173","author":"Boman","year":"2000","journal-title":"Immunol. Rev."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1073\/pnas.92.1.195","article-title":"FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis","volume":"92","author":"Agerberth","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1046\/j.1523-1747.2003.12069.x","article-title":"The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium","volume":"120","author":"Heilborn","year":"2003","journal-title":"J. Invest. Dermatol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/nm1407","article-title":"The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection","volume":"12","author":"Chromek","year":"2006","journal-title":"Nat. Med."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1084\/jem.192.7.1069","article-title":"LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells","volume":"192","author":"De Yang","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.4049\/jimmunol.176.5.3044","article-title":"An antimicrobial cathelicidin peptide, human CAP18\/LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptor-like 1 and P2X7","volume":"176","author":"Nagaoka","year":"2006","journal-title":"J. Immunol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.1128\/MCB.18.7.4301","article-title":"CCAAT\/enhancer binding protein \u03b1 is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors","volume":"18","author":"Radomska","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1182\/blood.V94.7.2310.419k34_2310_2318","article-title":"PU.1 and the granulocyte- and macrophage colony-stimulating factor receptors play distinct roles in late-stage myeloid cell differentiation","volume":"94","author":"Anderson","year":"1999","journal-title":"Blood"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1002\/jlb.66.6.989","article-title":"The individual regulation of granule protein mRNA levels during neutrophil maturation explains the heterogeneity of neutrophil granules","volume":"66","author":"Cowland","year":"1999","journal-title":"J. Leukoc. Biol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1084\/jem.189.11.1847","article-title":"Neutrophil-specific granule deficiency results from a novel mutation with loss of function of the transcription factor CCAAT\/enhancer binding protein \u03b5","volume":"189","author":"Lekstrom-Himes","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.4049\/jimmunol.173.5.2909","article-title":"Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression","volume":"173","author":"Wang","year":"2004","journal-title":"J. Immunol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1096\/fj.04-3284com","article-title":"Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3","volume":"19","author":"Gombart","year":"2005","journal-title":"FASEB J."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"1689S","DOI":"10.1093\/ajcn\/80.6.1689S","article-title":"Overview of general physiologic features and functions of vitamin D","volume":"80","author":"DeLuca","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1359\/JBMR.040511","article-title":"Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial","volume":"19","author":"Meier","year":"2004","journal-title":"J. Bone Miner. Res."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/S0022-3476(97)70068-4","article-title":"High incidence of significant bone loss in patients with severe congenital neutropenia (Kostmann\u2019s syndrome)","volume":"131","author":"Yakisan","year":"1997","journal-title":"J. Pediatr."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1111\/j.0022-202X.2005.23687.x","article-title":"Vitamin D induces the antimicrobial protein hCAP18 in human skin","volume":"124","author":"Weber","year":"2005","journal-title":"J. Invest. Dermatol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1182\/blood.V85.3.812.bloodjournal853812","article-title":"Biosynthesis of granule proteins in normal human bone marrow cells. Gelatinase is a marker of terminal neutrophil differentiation","volume":"85","author":"Borregaard","year":"1995","journal-title":"Blood"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0022-1759(99)00176-3","article-title":"Isolation of neutrophil precursors from bone marrow for biochemical and transcriptional analysis","volume":"232","author":"Cowland","year":"1999","journal-title":"J. Immunol. Methods"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1006\/bcmd.2002.0513","article-title":"Surface antigen changes during normal neutrophilic development: a critical review","volume":"28","author":"Elghetany","year":"2002","journal-title":"Blood Cells Mol. Dis."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/cyto.a.10104","article-title":"Immunophenotyping of acute leukemias and myelodysplastic syndromes","volume":"58","author":"Orfao","year":"2004","journal-title":"Cytometry A"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cyto.b.20008","article-title":"Immunophenotypic differentiation patterns of normal hematopoiesis in human bone marrow: reference patterns for age-related changes and disease-induced shifts","volume":"60","author":"Van Lochem","year":"2004","journal-title":"Cytometry B Clin. Cytom."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.1182\/blood.V96.9.3086","article-title":"The human antimicrobial and chemotactic peptides LL-37 and \u03b1-defensins are expressed by specific lymphocyte and monocyte populations","volume":"96","author":"Agerberth","year":"2000","journal-title":"Blood"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"456","DOI":"10.2144\/97233st02","article-title":"Design and testing of \u03b2-actin primers for RT-PCR that do not co-amplify processed pseudogenes","volume":"23","author":"Raff","year":"1997","journal-title":"Biotechniques"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1182\/blood.V90.7.2796","article-title":"The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils","volume":"90","author":"Sorensen","year":"1997","journal-title":"Blood"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1359\/JBMR.050908","article-title":"Immune regulation of 25-hydroxyvitamin-D3-1\u03b1-hydroxylase in human monocytes","volume":"21","author":"Stoffels","year":"2006","journal-title":"J. Bone Miner. Res."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"6816","DOI":"10.1038\/sj.onc.1210764","article-title":"Transcriptional control of granulocyte and monocyte development","volume":"26","author":"Friedman","year":"2007","journal-title":"Oncogene"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1532\/IJH97.A10407","article-title":"Marked reduction of LL-37\/hCAP-18, an antimicrobial peptide, in patients with acute myeloid leukemia","volume":"81","author":"An","year":"2005","journal-title":"Int. J. Hematol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.molimm.2007.04.023","article-title":"Complex regulation of human cathelicidin gene expression: novel splice variants and 5\u2019UTR negative regulatory element","volume":"45","author":"Elloumi","year":"2008","journal-title":"Mol. Immunol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"8218","DOI":"10.1073\/pnas.82.23.8218","article-title":"Phagocytic cells synthesize 19-nor-10-keto-25-hydroxyvitamin D3, a metabolite that may induce differentiation of the human monoblastic cell line U937","volume":"82","author":"Gray","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1172\/JCI113631","article-title":"Microbicidal\/cytotoxic proteins of neutrophils are deficient in two disorders: Chediak-Higashi syndrome and \u201cspecific\u201d granule deficiency","volume":"82","author":"Ganz","year":"1988","journal-title":"J. Clin. Invest."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/ng1170","article-title":"Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2","volume":"34","author":"Person","year":"2003","journal-title":"Nat. Genet."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.immuni.2007.12.020","article-title":"Mutations in growth factor independent-1 associated with human neutropenia block murine granulopoiesis through colony stimulating factor-1","volume":"28","author":"Zarebski","year":"2008","journal-title":"Immunity"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"4181","DOI":"10.1182\/blood-2005-05-022004","article-title":"Growth factor independence-1 (Gfi-1) plays a role in mediating specific granule deficiency (SGD) in a patient lacking a gene-inactivating mutation in the C\/EBP\u03b5 gene","volume":"109","author":"Khanna-Gupta","year":"2007","journal-title":"Blood"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/jlb.64.6.845","article-title":"Evaluation of the expression of human CAP18 gene during neutrophil maturation in the bone marrow","volume":"64","author":"Nagaoka","year":"1998","journal-title":"J. Leukoc. Biol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1210\/me.2003-0412","article-title":"1 \u03b1,25-Dihydroxyvitamin D3 transrepresses retinoic acid transcriptional activity via vitamin D receptor in myeloid cells","volume":"18","author":"Bastie","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1182\/blood.V87.7.2693.bloodjournal8772693","article-title":"1,25-Dihydroxyvitamin D3 differentiates normal neutrophilic promyelocytes to monocytes\/macrophages in vitro","volume":"87","author":"Nakamura","year":"1996","journal-title":"Blood"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1126\/science.1123933","article-title":"Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response","volume":"311","author":"Liu","year":"2006","journal-title":"Science"},{"key":"2023032712365131800_","doi-asserted-by":"crossref","first-page":"4406","DOI":"10.1182\/blood.V99.12.4406","article-title":"Induction of granulocytic differentiation by 2 pathways","volume":"99","author":"Zhang","year":"2002","journal-title":"Blood"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1189%2Fjlb.0607437","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/84\/5\/1279\/49611013\/jlb1279.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/84\/5\/1279\/49611013\/jlb1279.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T16:25:42Z","timestamp":1684513542000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/84\/5\/1279\/6975209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8,14]]},"references-count":48,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2008,8,14]]},"published-print":{"date-parts":[[2008,11,1]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.0607437","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"type":"print","value":"0741-5400"},{"type":"electronic","value":"1938-3673"}],"subject":[],"published-other":{"date-parts":[[2008,11]]},"published":{"date-parts":[[2008,8,14]]}}}