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We previously reported the infection of C3H 5\u2010lipoxygenase (LO)\u2010deficient mice with\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    results in prolonged nonresolving Lyme arthritis. Here we define the role of the 5\u2010LO metabolite leukotriene (LT)B\n                    <jats:sub>4<\/jats:sub>\n                    and its high\u2010affinity receptor, BLT1, in this response. C3H and C3H BLT1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were infected with\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    and arthritis progression was monitored by ankle swelling over time. Similar to 5\u2010LO\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, BLT1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice developed nonresolving Lyme arthritis characterized by increased neutrophils in the joint at later time points than WT mice, but with fewer apoptotic (caspase\u20103\n                    <jats:sup>+<\/jats:sup>\n                    ) neutrophils. In vitro, BLT1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    neutrophils were defective in their ability to undergo apoptosis due to the lack of LTB\n                    <jats:sub>4<\/jats:sub>\n                    \u2010mediated down\u2010regulation of cAMP, subsequent failure to induce Death\u2010Inducing Signaling Complex (DISC) components, and decreased FasL and CD36 expression. Inhibition of adenylyl cyclase with SQ 22,536 restored BLT1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    BMN apoptosis, FasL and CD36 expression, and clearance by macrophages. We conclude that LTB4\/BLT1 signaling has an unexpected critical role in mediating neutrophil apoptosis via the down\u2010regulation of cAMP. Loss of BLT1 signaling led to defective clearance of neutrophils from the inflamed joint and failed arthritis resolution.\n                  <\/jats:p>","DOI":"10.1096\/fj.201902014r","type":"journal-article","created":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T06:41:15Z","timestamp":1577169675000},"page":"2840-2852","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Leukotriene B4 receptor BLT1 signaling is critical for neutrophil apoptosis and resolution of experimental Lyme arthritis"],"prefix":"10.1096","volume":"34","author":[{"given":"Kinsey A.","family":"Hilliard","sequence":"first","affiliation":[{"name":"Department of Pathobiology College of Veterinary Medicine, University of Missouri Columbia MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria A.","family":"Blaho","sequence":"additional","affiliation":[{"name":"Immunity and Pathogenesis Program Sanford Burnham Prebys Medical Discovery Institute San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christa D.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Pathobiology College of Veterinary Medicine, University of Missouri Columbia MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles R.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Pathobiology College of Veterinary Medicine, University of Missouri Columbia MO 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