{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:31:16Z","timestamp":1790699476757,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Polytraumatized patients undergo a strong immunological stress upon insult. Phagocytes (granulocytes and monocytes) play a substantial role in immunological defense against bacteria, fungi and yeast, and in the clearance of cellular debris after tissue injury. We have reported a reduced monocytes phagocytic activity early after porcine polytrauma before. However, it is unknown if both phagocyte types undergo those functional alterations, and if there is a pathogen-specific phagocytic behavior. We characterized the phagocytic activity and capacity of granulocytes and monocytes after polytrauma.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Eight pigs (<jats:italic>Sus scrofa<\/jats:italic>) underwent polytrauma consisting of lung contusion, liver laceration, tibial fracture and hemorrhagic shock with fluid resuscitation and fracture fixation with external fixator. Intensive care treatment including mechanical ventilation for 72 h followed. Phagocytic activity and capacity were investigated using an <jats:italic>in vitro ex vivo<\/jats:italic> whole blood stimulation phagocytosis assays before trauma, after surgery, 24, 48, and 72 h after trauma. Blood samples were stimulated with Phorbol-12-myristate-13-acetate and incubated with FITC-labeled <jats:italic>E. coli, S. aureus<\/jats:italic> or <jats:italic>S. cerevisiae<\/jats:italic> for phagocytosis assessment by flow cytometry.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Early polytrauma-induced significant increase of granulocytes and monocytes declined to baseline values within 24 h. Percentage of <jats:italic>E. coli<\/jats:italic>-phagocytizing granulocytes significantly decreased after polytrauma and during further intensive care treatment, while their capacity significantly increased. Interestingly, both granulocytic phagocytic activity and capacity of <jats:italic>S. aureus<\/jats:italic> significantly decreased after trauma, although a recovery was observed after 24 h and yet was followed by another decrease. The percentage of <jats:italic>S. cerevisiae<\/jats:italic>-phagocytizing granulocytes significantly increased after 24 h, while their impaired capacity after surgery and 72 h later was detected. Monocytic <jats:italic>E. coli<\/jats:italic>-phagocytizing percentage did not change, while their capacity increased after 24\u201372 h. After a significant decrease in <jats:italic>S. aureus<\/jats:italic>-phagocytizing monocytes after surgery, a significant increase after 24 and 48 h was observed without capacity alterations. No significant changes in <jats:italic>S. cerevisiae<\/jats:italic>-phagocytizing monocytes occurred, but their capacity dropped 48 and 72 h.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Phagocytic activity and capacity of granulocytes and monocytes follow a different pattern and significantly change within 72 h after polytrauma. Both phagocytic activity and capacity show significantly different alterations depending on the pathogen strain, thus potentially indicating at certain and possibly more relevant infection causes after polytrauma.<\/jats:p>","DOI":"10.3389\/fmed.2021.645589","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T04:50:12Z","timestamp":1617684612000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Alterations of Phagocytic Activity and Capacity in Granulocytes and Monocytes Depend on the Pathogen Strain in Porcine Polytrauma"],"prefix":"10.3389","volume":"8","author":[{"given":"Jan Tilmann","family":"Vollrath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Klingebiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix Marius","family":"Bl\u00e4sius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Greven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eftychios","family":"Bolierakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Janicova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildiko Rita","family":"Dunay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Hildebrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Marzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borna","family":"Relja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"B1","volume-title":"Global Health Estimates 2016: Disease Burden by Cause, Age, Sex, by Country and by Region, 2000-2016","year":"2018"},{"key":"B2","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1097\/00005373-200111000-00003","article-title":"Multiple organ failure still a major cause of morbidity but not mortality in blunt multiple trauma","volume":"51","author":"Nast-Kolb","year":"2001","journal-title":"J Trauma."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00068-019-01235-w","article-title":"Damage-associated molecular patterns in trauma","volume":"324","author":"Relja","year":"2019","journal-title":"Eur J Trauma Emerg Surg."},{"key":"B4","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1097\/TA.0b013e3181bbfe2a","article-title":"Trauma mortality in mature trauma systems: are we doing better? An analysis of trauma mortality patterns, 1997-2008","volume":"69","author":"Dutton","year":"2010","journal-title":"J Trauma."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.3171\/2013.8.JNS13276","article-title":"Marked reduction in mortality in patients with severe traumatic brain injury","volume":"119","author":"Gerber","year":"2013","journal-title":"J Neurosurg."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2234","DOI":"10.1097\/01.CCM.0000145586.23276.0F","article-title":"Epidemiology of sepsis in patients with traumatic injury","volume":"32","author":"Osborn","year":"2004","journal-title":"Crit Care Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1097\/CCM.0000000000002577","article-title":"Phenotyping the immune response to trauma","volume":"45","author":"Seshadri","year":"2017","journal-title":"Crit Care Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1089\/neu.2017.5399","article-title":"Chronic alterations in systemic immune function after traumatic brain injury","volume":"35","author":"Ritzel","year":"2018","journal-title":"J Neurotrauma."},{"key":"B9","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/nri3399","article-title":"Neutrophil recruitment and function in health and inflammation","volume":"13","author":"Kolaczkowska","year":"2013","journal-title":"Nat Rev Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1146\/annurev-biochem-060815-014442","article-title":"Reactive oxygen species and neutrophil function","volume":"85","author":"Winterbourn","year":"2016","journal-title":"Annu Rev Biochem."},{"key":"B11","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1002\/cyto.b.21280","article-title":"Monocytes and macrophages in flow: an ESCCA initiative on advanced analyses of monocyte lineage using flow cytometry","volume":"92","author":"Lambert","year":"2017","journal-title":"Cytometry B Clin Cytom."},{"key":"B12","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1055\/s-0029-1243375","article-title":"Krankenhaushygiene \u2013 nosokomiale infektionen","volume":"45","author":"Kerwat","year":"2010","journal-title":"An\u00e4sthesiol Intensivmed Notfallmed Schmerzther."},{"key":"B13","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1097\/00005373-199911000-00018","article-title":"Infection in hospitalized trauma patients: incidence, risk factors, and complications","volume":"47","author":"Papia","year":"1999","journal-title":"J Trauma."},{"key":"B14","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1146\/annurev-pathol-011811-132445","article-title":"The cell biology of phagocytosis","volume":"7","author":"Flannagan","year":"2012","journal-title":"Annu Rev Pathol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/j.1365-2249.2008.03737.x","article-title":"Prognostic value of phagocytic activity of neutrophils and monocytes in sepsis. Correlation to CD64 and CD14 antigen expression","volume":"154","author":"Danikas","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1097\/00024382-200116020-00003","article-title":"Overexpression of the high-affinity Fcgamma receptor (CD64) is associated with leukocyte dysfunction in sepsis","volume":"16","author":"Hirsh","year":"2001","journal-title":"Shock."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1086\/317499","article-title":"Relationship between interleukin-6 plasma concentration in patients with sepsis, monocyte phenotype, monocyte phagocytic properties, and cytokine production","volume":"31","author":"Spittler","year":"2000","journal-title":"Clin Infect Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.imbio.2016.09.010","article-title":"Phagocytizing activity of PMN from severe trauma patients in different post-traumatic phases during the 10-days post-injury course","volume":"222","author":"Sturm","year":"2017","journal-title":"Immunobiology."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0187404","DOI":"10.1371\/journal.pone.0187404","article-title":"Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model","volume":"12","author":"Schimunek","year":"2017","journal-title":"PLoS ONE."},{"key":"B20","volume-title":"Guide for the Care and Use of Laboratory Animals.","year":"2011"},{"key":"B21","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.joca.2012.02.010","article-title":"Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research","volume":"20","author":"Kilkenny","year":"2012","journal-title":"Osteoarthr Cartil."},{"key":"B22","doi-asserted-by":"publisher","first-page":"39659","DOI":"10.1038\/srep39659","article-title":"Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma","volume":"6","author":"Horst","year":"2016","journal-title":"Sci Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1097\/01586154-201305000-00026","article-title":"Advanced trauma life support (ATLS\u00ae): the ninth edition","volume":"74","year":"2013","journal-title":"J Trauma Acute Care Surg."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e121","DOI":"10.1016\/j.resuscitation.2015.07.043","article-title":"Part 5: Acute coronary syndromes: 2015 International consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations","volume":"95","author":"Nikolaou","year":"2015","journal-title":"Resuscitation."},{"key":"B25","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1016\/j.injury.2009.05.006","article-title":"Patterns of mortality and causes of death in polytrauma patients\u2013has anything changed?","volume":"40","author":"Pfeifer","year":"2009","journal-title":"Injury."},{"key":"B26","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s00068-018-0962-3","article-title":"Danger signals in trauma","volume":"44","author":"Relja","year":"2018","journal-title":"Eur J Trauma Emerg Surg."},{"key":"B27","first-page":"1004","article-title":"Evaluation of patients with leukocytosis","volume":"92","author":"Riley","year":"2015","journal-title":"Am Fam Physician."},{"key":"B28","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1097\/MCP.0b013e32835f27be","article-title":"Hospital-acquired pneumonia and ventilator-associated pneumonia","volume":"19","author":"Barbier","year":"2013","journal-title":"Curr Opin Pulm Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.4049\/jimmunol.1500984","article-title":"A detailed characterization of the dysfunctional immunity and abnormal myelopoiesis induced by severe shock and trauma in the aged","volume":"195","author":"Nacionales","year":"2015","journal-title":"J Immunol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.vph.2015.02.006","article-title":"Ticagrelor potentiates adenosine-induced stimulation of neutrophil chemotaxis and phagocytosis","volume":"71","author":"Alsharif","year":"2015","journal-title":"Vascul Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.intimp.2014.09.030","article-title":"Regulation of neutrophil phagocytosis of Escherichia coli by antipsychotic drugs","volume":"23","author":"Chen","year":"2014","journal-title":"Int Immunopharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1136\/thoraxjnl-2017-211323","article-title":"Randomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosis","volume":"73","author":"Pinder","year":"2018","journal-title":"Thorax."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1128\/IAI.69.4.2011-2016.2001","article-title":"Leukotriene B4 augments neutrophil phagocytosis of Klebsiella pneumoniae","volume":"69","author":"Mancuso","year":"2001","journal-title":"Infect Immun"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1128\/AAC.02409-18","article-title":"Antifungal drugs influence neutrophil effector functions","volume":"63","author":"Ries","year":"2019","journal-title":"Antimicrob Agents Chemother."},{"key":"B35","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40635-020-0299-1","article-title":"New automated analysis to monitor neutrophil function point-of-care in the intensive care unit after trauma","volume":"8","author":"Hesselink","year":"2020","journal-title":"Intensive Care Med Exp."},{"key":"B36","first-page":"38","article-title":"Phagocytic response of bovine polymorphonuclear leukocytes to different incubation conditions and following exposure to some effectors of phagocytosis and different anticoagulants in vitro","volume":"65","author":"Ducusin","year":"2001","journal-title":"Can J Vet Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/cc9388","article-title":"Lack of effect of glutamine administration to boost the innate immune system response in trauma patients in the intensive care unit","volume":"14","author":"Perez-Barcena","year":"2010","journal-title":"Crit Care."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e68963","DOI":"10.1371\/journal.pone.0068963","article-title":"Oxidative burst of circulating neutrophils following traumatic brain injury in human","volume":"8","author":"Liao","year":"2013","journal-title":"PLoS ONE."},{"key":"B39","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.apmr.2012.09.015","article-title":"Phagocytic and oxidative burst activity of neutrophils in patients with spinal cord injury","volume":"94","author":"Kanyilmaz","year":"2013","journal-title":"Arch Phys Med Rehabil."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1016\/j.injury.2014.06.021","article-title":"The impact of trauma on neutrophil function","volume":"45","author":"Hazeldine","year":"2014","journal-title":"Injury."},{"key":"B41","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1053\/srin.2000.20935","article-title":"Trauma, head injury, and neurosurgery infections","volume":"15","author":"Boque","year":"2000","journal-title":"Semin Respir Infect."},{"key":"B42","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.ijid.2017.07.002","article-title":"Invasive fungal infections secondary to traumatic injury","volume":"62","author":"Kronen","year":"2017","journal-title":"Int J Infect Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"649","DOI":"10.3892\/ijmm.17.4.649","article-title":"Self-regulation of neutrophils during phagocytosis is modified after severe tissue injury","volume":"17","author":"Pap","year":"2006","journal-title":"Int J Mol Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"L379","DOI":"10.1152\/ajplung.00010.2008","article-title":"Animal models of acute lung injury","volume":"295","author":"Matute-Bello","year":"2008","journal-title":"Am J Physiol Lung Cell Mol Physiol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.645589\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T04:50:18Z","timestamp":1617684618000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.645589\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,6]]},"references-count":44,"alternative-id":["10.3389\/fmed.2021.645589"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.645589","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,6]]},"article-number":"645589"}}