{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T02:52:44Z","timestamp":1780541564308,"version":"3.54.1"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              <jats:italic>Nbeal2<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, a model of human gray platelet syndrome, have reduced neutrophil granularity and impaired host defense against systemic\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              infection. We here aimed to study the role of Nbeal2 deficiency in both leukocytes and platelets during gram-negative pneumonia and sepsis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              We studied the role of\n              <jats:italic>Nbeal2<\/jats:italic>\n              in platelets and leukocytes during murine pneumonia and sepsis by\n              <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n              . Apart from platelet \u03b1-granule deficiency and reduced neutrophil granularity, also monocyte granularity was reduced in\n              <jats:italic>Nbeal2<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, whereas plasma levels of MPO (myeloperoxidase), elastase, NGAL (neutrophil gelatinase\u2013associated lipocalin), and MMP-9 (matrix metalloproteinase 9), and leukocyte CD11b expression were increased.\n              <jats:italic>Nbeal2<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              leukocytes showed unaltered in vitro antibacterial response and phagocytosis capacity against\n              <jats:italic>Klebsiella<\/jats:italic>\n              , and unchanged reactive nitrogen species and cytokine production. Also during\n              <jats:italic>Klebsiella<\/jats:italic>\n              pneumonia and sepsis,\n              <jats:italic>Nbeal2<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice had similar bacterial growth in lung and distant body sites, with enhanced leukocyte migration to the bronchoalveolar space. Despite similar infection-induced inflammation, organ damage was increased in\n              <jats:italic>Nbeal2<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>mice<\/jats:italic>\n              , which was also seen during endotoxemia. Platelet-specific\n              <jats:italic>Nbeal2<\/jats:italic>\n              deficiency did not influence leukocyte functions, indicating that\n              <jats:italic>Nbeal2<\/jats:italic>\n              directly modifies leukocytes. Transfusion of\n              <jats:italic>Nbeal2<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              but not of\n              <jats:italic>Nbeal2<\/jats:italic>\n              <jats:sup>+\/+<\/jats:sup>\n              platelets into thrombocytopenic mice was associated with bleeding in the lung but similar host defense, pointing at a role for platelet \u03b1-granules in maintaining vascular integrity but not host defense during\n              <jats:italic>Klebsiella<\/jats:italic>\n              pneumosepsis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              These data show that\n              <jats:italic>Nbeal2<\/jats:italic>\n              deficiency\u2014resulting in gray platelet syndrome\u2014affects platelets, neutrophils, and monocytes, with intact host defense but increased organ damage during gram-negative pneumosepsis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.118.311332","type":"journal-article","created":{"date-parts":[[2018,6,21]],"date-time":"2018-06-21T09:00:47Z","timestamp":1529571647000},"page":"1772-1784","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["<i>Nbeal2<\/i>\n            Deficiency Increases Organ Damage but Does Not Affect Host Defense During Gram-Negative Pneumonia-Derived Sepsis"],"prefix":"10.1161","volume":"38","author":[{"given":"Theodora A.M.","family":"Claushuis","sequence":"first","affiliation":[{"name":"From the Center for Experimental and Molecular Medicine (T.A.M.C., S.F.d.S., A.F.d.V., C.v.V., T.v.d.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha F.","family":"de Stoppelaar","sequence":"additional","affiliation":[{"name":"From the Center for Experimental and Molecular Medicine (T.A.M.C., S.F.d.S., A.F.d.V., C.v.V., T.v.d.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex F.","family":"de Vos","sequence":"additional","affiliation":[{"name":"From the Center for Experimental and Molecular Medicine (T.A.M.C., S.F.d.S., A.F.d.V., C.v.V., T.v.d.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita E.","family":"Grootemaat","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam, The Netherlands; Electron Microscopy Center Amsterdam, Medical Biology, Academic Medical Center, The Netherlands (A.E.G., N.N.v.d.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole N.","family":"van der Wel","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam, The Netherlands; Electron Microscopy Center Amsterdam, Medical Biology, Academic Medical Center, The Netherlands (A.E.G., N.N.v.d.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris 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