{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:29:19Z","timestamp":1790267359726,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2003,5,1]],"date-time":"2003-05-01T00:00:00Z","timestamp":1051747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Association","doi-asserted-by":"publisher","award":["SFB293\/A8"],"award-info":[{"award-number":["SFB293\/A8"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Interdisciplinary Center of Clinical Research"},{"name":"German Ministry of Research","award":["IZKF-C2, D15"],"award-info":[{"award-number":["IZKF-C2, D15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mice with a naturally occurring Csfmop\/Csfmop (op\/op) gene mutation lack functional macrophage-colony stimulating factor (M-CSF) and are deficient of M-CSF-derived macrophages. They are severely monocytopenic, and their remaining M-CSF-independent macrophages were shown to differ in differentiation and distinct functions when compared with phenotypicaly normal mice of the same background. It is not known if osteopetrosis mice (op\/op mice) are able to mount a specific immune response against intracellular pathogens, as this would require complex effector functions by macrophages. We therefore investigated the ability of op\/op mice and their M-CSF-independent macrophages to combat infection with Leishmania major. op\/op mice retained the ability to resist an infection with L. major by mounting a T helper cell type 1 cell response, eliminating parasites and resolving the lesions. Macrophages from op\/op mice were able to sufficiently perform effector functions in vitro, such as phagocytosis, production of leishmanicidal nitric oxide (NO), killing of parasites, and release of interleukin (IL)-12. There were quantitative differences, as M-CSF-derived macrophages from hematopoietic organs of control mice showed significantly higher rates of phagocytosis and higher NO release after stimulation with lipopolysaccharides than corresponding macrophages from op\/op mice. In contrast, when peritoneally elicited macrophages were used, those from op\/op mice revealed a stronger response than those from control mice with regard to release of NO or IL-12. These differences suggest that M-CSF-independent maturation of op\/op monocytes subsequent to their release from hematopoietic tissue exerts influence on their effector functions. However, M-CSF or M-CSF-derived macrophages are not necessary for an effective immune response against L. major.<\/jats:p>","DOI":"10.1189\/jlb.12011003","type":"journal-article","created":{"date-parts":[[2003,4,24]],"date-time":"2003-04-24T15:20:31Z","timestamp":1051197631000},"page":"564-573","source":"Crossref","is-referenced-by-count":21,"title":["Monocyte and macrophage functions in M-CSF-deficient\n                    <i>op\/op<\/i>\n                    mice during experimental leishmaniasis"],"prefix":"10.1093","volume":"73","author":[{"given":"Frank","family":"Sch\u00f6nlau","sequence":"first","affiliation":[{"name":"Institute of Experimental Dermatology, University of M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Schlesiger","sequence":"additional","affiliation":[{"name":"Institute of Experimental Dermatology, University of M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Ehrehen","sequence":"additional","affiliation":[{"name":"Institute of Experimental Dermatology, University of M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Grabbe","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Sorg","sequence":"additional","affiliation":[{"name":"Institute of Experimental Dermatology, University of M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cord","family":"Sunderk\u00f6tter","sequence":"additional","affiliation":[{"name":"Institute of Experimental Dermatology, University of M\u00fcnster , Germany"},{"name":"Department of Dermatology, University of M\u00fcnster , Germany"},{"name":"Department of Dermatology, University of Ulm , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,5,1]]},"reference":[{"key":"2023033018584268800_jlb0564-cit-B1","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1152\/physrev.1996.76.4.927","article-title":"Cytokine regulation of the macrophage (M) system studied using the colony stimulating factor-1-deficient op\/op mouse","volume":"76","author":"Wiktor-Jedrzejczak","year":"1996","journal-title":"Physiol. Rev."},{"key":"2023033018584268800_jlb0564-cit-B2","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/jlb.53.5.602","article-title":"Mechanisms generating functionally heterogeneous macrophages: chaos revisited","volume":"53","author":"Rutherford","year":"1993","journal-title":"J. Leukoc. Biol."},{"key":"2023033018584268800_jlb0564-cit-B3","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/S0092-8674(00)80290-1","article-title":"Enforced expression of Bcl-2 in monocytes rescues macrophages and partially reverses osteopetrosis in op\/op mice","volume":"89","author":"Lagasse","year":"1997","journal-title":"Cell"},{"key":"2023033018584268800_jlb0564-cit-B4","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/S0092-8674(85)80047-7","article-title":"The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1","volume":"41","author":"Sherr","year":"1985","journal-title":"Cell"},{"key":"2023033018584268800_jlb0564-cit-B5","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1182\/blood.V99.1.111","article-title":"Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects","volume":"99","author":"Dai","year":"2002","journal-title":"Blood"},{"key":"2023033018584268800_jlb0564-cit-B6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1182\/blood.V89.1.65","article-title":"Cytokine receptor expression on hematopoietic stem and progenitor cells","volume":"89","author":"McKinstry","year":"1997","journal-title":"Blood"},{"key":"2023033018584268800_jlb0564-cit-B7","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1182\/blood-2001-12-0235","article-title":"Identification of primary structural features that define the differential actions of IL-3 and GM-CSF receptors","volume":"100","author":"Evans","year":"2002","journal-title":"Blood"},{"key":"2023033018584268800_jlb0564-cit-B8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/jlb.51.1.69","article-title":"Differential immunocompetence of macrophages derived using macrophage or granulocyte-macrophage colony-stimulating factor","volume":"51","author":"Rutherford","year":"1992","journal-title":"J. Leukoc. Biol."},{"key":"2023033018584268800_jlb0564-cit-B9","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/jlb.43.2.148","article-title":"Comparison of bone marrow progenitors responsive to granulocyte-macrophage colony stimulating factor and macrophage colony-stimulating factor-1","volume":"43","author":"Falk","year":"1988","journal-title":"J. Leukoc. Biol."},{"key":"2023033018584268800_jlb0564-cit-B10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/oxfordjournals.jhered.a108657","article-title":"Osteopetrosis, a new recessive skeletal mutation on chromosome 12 of the mouse","volume":"67","author":"Marks","year":"1976","journal-title":"J. Hered."},{"key":"2023033018584268800_jlb0564-cit-B11","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/345442a0","article-title":"The murine mutation osteopetrosis is in the coding region of the macrophage colony-stimulating factor gene","volume":"345","author":"Yoshida","year":"1990","journal-title":"Nature"},{"key":"2023033018584268800_jlb0564-cit-B12","first-page":"657","article-title":"Abnormal differentiation of tissue macrophage populations in \u2018osteopetrosis\u2019 (op) mice defective in the production of macrophage colony-stimulating factor","volume":"139","author":"Naito","year":"1991","journal-title":"Am. J. Pathol."},{"key":"2023033018584268800_jlb0564-cit-B13","first-page":"1004","article-title":"CSF-1 deficiency in the op\/op mouse has differential effects on macrophage populations and differentiation stages","volume":"20","author":"Wiktor-Jedrzejczak","year":"1992","journal-title":"Exp. Hematol."},{"key":"2023033018584268800_jlb0564-cit-B14","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/(SICI)1098-2795(199701)46:1<85::AID-MRD13>3.0.CO;2-2","article-title":"Macrophage differentiation and granulomatous inflammation in osteopetrotic mice (op\/op) defective in the production of CSF-1","volume":"46","author":"Naito","year":"1997","journal-title":"Mol. Reprod. Dev."},{"key":"2023033018584268800_jlb0564-cit-B15","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1210\/endo.134.4.8137761","article-title":"Granulocyte-macrophage colony-stimulating factor corrects macrophage deficiencies, but not osteopetrosis, in the colony-stimulating factor 1-deficient op\/op mouse","volume":"134","author":"Wiktor-Jedrzejczak","year":"1994","journal-title":"Endocrinology"},{"key":"2023033018584268800_jlb0564-cit-B16","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0002-9440(10)65301-1","article-title":"Granulocyte\/macrophage colony-stimulating factor and interleukin-3 correct osteopetrosis in mice with osteopetrosis mutation","volume":"154","author":"Myint","year":"1999","journal-title":"Am. J. Pathol."},{"key":"2023033018584268800_jlb0564-cit-B17","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1006\/cimm.1995.1062","article-title":"Osteopetrotic (op\/op) mice deficient in macrophages have the ability to mount a normal T-cell-dependent immune response","volume":"162","author":"Chang","year":"1995","journal-title":"Cell. Immunol."},{"key":"2023033018584268800_jlb0564-cit-B18","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1128\/iai.64.5.1577-1581.1996","article-title":"Colony-stimulating factor 1-dependent resident macrophages play a regulatory role in fighting Escherichia coli fecal peritonitis","volume":"64","author":"Wiktor-Jedrzejczak","year":"1996","journal-title":"Infect. Immun."},{"key":"2023033018584268800_jlb0564-cit-B19","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1002\/eji.1830220743","article-title":"Distinct in vivo functions of two macrophage subpopulations as evidenced by studies using macrophage-deficient op\/op mouse","volume":"22","author":"Wiktor-Jedrzejczak","year":"1992","journal-title":"Eur. J. Immunol."},{"key":"2023033018584268800_jlb0564-cit-B20","doi-asserted-by":"crossref","first-page":"4891","DOI":"10.4049\/jimmunol.151.9.4891","article-title":"Resistance of mice to experimental leishmaniasis is associated with more rapid appearance of mature macrophages in vitro and in vivo","volume":"151","author":"Sunderk\u00f6tter","year":"1993","journal-title":"J. Immunol."},{"key":"2023033018584268800_jlb0564-cit-B21","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0952-7915(96)80040-9","article-title":"Invasion, control and persistence of Leishmania parasites","volume":"8","author":"Bogdan","year":"1996","journal-title":"Curr. Opin. Immunol."},{"key":"2023033018584268800_jlb0564-cit-B22","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1002\/(SICI)1521-4141(199907)29:07<2319::AID-IMMU2319>3.0.CO;2-3","article-title":"Susceptibility or resistance to Leishmania infection is dictated by the macrophages evolved under the influence of IL-3 or GM-CSF","volume":"29","author":"Saha","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"2023033018584268800_jlb0564-cit-B23","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/S1286-4579(00)01267-3","article-title":"Mice unresponsive to GM-CSF are unexpectedly resistant to cutaneous Leishmania major infection","volume":"2","author":"Scott","year":"2000","journal-title":"Microbes Infect."},{"key":"2023033018584268800_jlb0564-cit-B24","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev.iy.13.040195.001055","article-title":"The regulation of immunity to Leishmania major","volume":"13","author":"Reiner","year":"1995","journal-title":"Annu. Rev. Immunol."},{"key":"2023033018584268800_jlb0564-cit-B25","doi-asserted-by":"crossref","first-page":"4378","DOI":"10.1128\/iai.65.11.4378-4383.1997","article-title":"Interleukin-12 is indispensable for protective immunity against Leishmania major","volume":"65","author":"Mattner","year":"1997","journal-title":"Infect. Immun."},{"key":"2023033018584268800_jlb0564-cit-B26","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1002\/eji.1830211216","article-title":"Resistance to Leishmania major infection correlates with the induction of nitric oxide synthase in murine macrophages","volume":"21","author":"Liew","year":"1991","journal-title":"Eur. J. Immunol."},{"key":"2023033018584268800_jlb0564-cit-B27","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/375408a0","article-title":"Altered immune responses in mice lacking inducible nitric oxide synthase","volume":"375","author":"Wei","year":"1995","journal-title":"Nature"},{"key":"2023033018584268800_jlb0564-cit-B28","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/eji.1830250310","article-title":"Dendritic cells in Leishmania major-immune mice harbor persistent parasites and mediate an antigen-specific T cell immune response","volume":"25","author":"Moll","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"2023033018584268800_jlb0564-cit-B29","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1002\/1521-4141(200009)30:9<2729::AID-IMMU2729>3.0.CO;2-3","article-title":"In experimental leishmaniasis deficiency of CD18 results in parasite dissemination associated with altered macrophage functions and incomplete Th1 cell response","volume":"30","author":"Sch\u00f6nlau","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"2023033018584268800_jlb0564-cit-B30","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.4049\/jimmunol.141.7.2407","article-title":"Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages","volume":"141","author":"Ding","year":"1988","journal-title":"J. Immunol."},{"key":"2023033018584268800_jlb0564-cit-B31","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/j.1365-3024.1985.tb00098.x","article-title":"A limiting dilution assay for quantifying Leishmania major in tissues of infected mice","volume":"7","author":"Titus","year":"1985","journal-title":"Parasite Immunol."},{"key":"2023033018584268800_jlb0564-cit-B32","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0022-1759(94)90005-1","article-title":"Markers of mouse macrophage development detected by monoclonal antibodies","volume":"174","author":"Leenen","year":"1994","journal-title":"J. Immunol. Methods"},{"key":"2023033018584268800_jlb0564-cit-B33","first-page":"74","article-title":"A new monoclonal antibody against Leishmania major parasites","volume":"285","author":"Kunz","year":"1993","journal-title":"Arch. Dermatol. Res."},{"key":"2023033018584268800_jlb0564-cit-B34","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1002\/eji.1830260725","article-title":"Activated T cells induce expression of E-selectin in vitro and in an antigen-dependent manner in vivo","volume":"26","author":"Sunderk\u00f6tter","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"2023033018584268800_jlb0564-cit-B35","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1084\/jem.179.6.1885","article-title":"Antigen-specific activation, tolerization, and reactivation of the interleukin 4 pathway in vivo","volume":"179","author":"R\u00f6cken","year":"1994","journal-title":"J. Exp. Med."},{"key":"2023033018584268800_jlb0564-cit-B36","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1084\/jem.181.5.1615","article-title":"Early interleukin 12 production by macrophages in response to mycobacterial infection depends on interferon and tumor necrosis factor","volume":"181","author":"Flesch","year":"1995","journal-title":"J. Exp. Med."},{"key":"2023033018584268800_jlb0564-cit-B37","first-page":"1","article-title":"Cell biology of mononuclear phagocytes","author":"Van Furth","year":"1993"},{"key":"2023033018584268800_jlb0564-cit-B38","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/jlb.48.1.43","article-title":"Differential production of IFN-alpha\/beta by CSF-1- and GM-CSF-derived macrophages. J","volume":"48","author":"Falk","year":"1990","journal-title":"Leukoc. Biol."},{"key":"2023033018584268800_jlb0564-cit-B39","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/978-1-4615-2930-9_49","article-title":"Immunophenotypic and ultrastructural differentiation and maturation of nonlymphoid dendritic cells in osteopetrotic (op) mice with the total absence of macrophage colony-stimulating factor activity","volume":"329","author":"Takahashi","year":"1993","journal-title":"Adv. Exp. Med. Biol."},{"key":"2023033018584268800_jlb0564-cit-B40","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/jlb.53.1.19","article-title":"Differentiation of dendritic cell populations in macrophage colony-stimulating factor-deficient mice homozygous for the osteopetrosis (op) mutation","volume":"53","author":"Takahashi","year":"1993","journal-title":"J. Leukoc. Biol."},{"key":"2023033018584268800_jlb0564-cit-B41","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1002\/jbmr.5650050716","article-title":"Impairment of macrophage colony-stimulating factor production and lack of resident bone marrow macrophages in the osteopetrotic op\/op mouse","volume":"5","author":"Felix","year":"1990","journal-title":"J. Bone Miner. Res."},{"key":"2023033018584268800_jlb0564-cit-B42","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1084\/jem.173.1.269","article-title":"Congenital osteoclast deficiency in osteopetrotic (op\/op) mice is cured by injections of macrophage colony-stimulating factor","volume":"173","author":"Kodama","year":"1991","journal-title":"J. Exp. Med."}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1189%2Fjlb.12011003","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/73\/5\/564\/49660817\/jlb0564.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/73\/5\/564\/49660817\/jlb0564.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T19:32:43Z","timestamp":1680204763000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/73\/5\/564\/6979409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,5,1]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2003,5,1]]},"published-print":{"date-parts":[[2003,5,1]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.12011003","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,5]]},"published":{"date-parts":[[2003,5,1]]}}}