{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:13:16Z","timestamp":1791162796613,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2007,8,3]],"date-time":"2007-08-03T00:00:00Z","timestamp":1186099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Surgical Infection Society"},{"DOI":"10.13039\/100005301","name":"American College of Surgeons","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Phagocytosis is the process by which microbial pathogens are engulfed by macrophages and neutrophils and represents the first line of defense against bacterial infection. The importance of phagocytosis for bacterial clearance is of particular relevance to systemic inflammatory diseases, which are associated with the development of hypoxia, yet the precise effects of hypoxia on phagocytosis remain largely unexplored. We now hypothesize that hypoxia inhibits phagocytosis in macrophages and sought to determine the mechanisms involved. Despite our initial prediction, hypoxia significantly increased the phagocytosis rate of particles in vitro by RAW264.7 and primary peritoneal macrophages and increased phagocytosis of labeled bacteria in vivo by hypoxic mice compared with normoxic controls. In understanding the mechanisms involved, hypoxia caused no changes in RhoA-GTPase signaling but increased the phosphorylation of p38-MAPK significantly. Inhibition of p38 reversed the effects of hypoxia on phagocytosis, suggesting a role for p38 in the hypoxic regulation of phagocytosis. Hypoxia also significantly increased the expression of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) in macrophages, which was reversed after p38 inhibition, suggesting a link between p38 activation and HIF-1\u03b1 expression. It is striking that small interfering RNA knockdown of HIF-1\u03b1 reversed the effects of hypoxia on phagocytosis, and overexpression of HIF-1\u03b1 caused a surprising increase in phagocytosis compared with nontransfected controls, demonstrating a specific role for HIF-1\u03b1 in the regulation of phagocytosis. These data indicate that hypoxia enhances phagocytosis in macrophages in a HIF-1\u03b1-dependent manner and shed light on an important role for HIF-1\u03b1 in host defense.<\/jats:p>","DOI":"10.1189\/jlb.0307195","type":"journal-article","created":{"date-parts":[[2007,8,4]],"date-time":"2007-08-04T01:45:03Z","timestamp":1186191903000},"page":"1257-1265","source":"Crossref","is-referenced-by-count":172,"title":["Hypoxia causes an increase in phagocytosis by macrophages in a HIF-1\u03b1-dependent manner"],"prefix":"10.1093","volume":"82","author":[{"given":"Rahul J","family":"Anand","sequence":"first","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, and University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C","family":"Gribar","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, and University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, and University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff W","family":"Kohler","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, and University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria F","family":"Branca","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, and University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Dubowski","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, and University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chhinder P","family":"Sodhi","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, and University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Hackam","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, and University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,8,3]]},"reference":[{"key":"2023033006495234100_","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1083\/jcb.124.5.677","article-title":"Biogenesis of phagolysosomes proceeds through a sequential series of interactions with the endocytic apparatus","volume":"124","author":"Desjardins","year":"1994","journal-title":"J. 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