title: Severe Acinetobacter baumannii sepsis is associated with elevation of pentraxin 3.
abstract: Multidrug-resistant Acinetobacter baumannii is among the most prevalent bacterial pathogens associated with trauma-related wound and bloodstream infections. Although septic shock and disseminated intravascular coagulation have been reported following fulminant A. baumannii sepsis, little is known about the protective host immune response to this pathogen. In this study, we examined the role of PTX3, a soluble pattern recognition receptor with reported antimicrobial properties and stored within neutrophil granules. PTX3 production by murine J774a.1 macrophages was assessed following challenge with A. baumannii strains ATCC 19606 and clinical isolates (CI) 77, 78, 79, 80, and 86. Interestingly, only CI strains 79, 80, and 86 induced PTX3 synthesis in murine J774a.1 macrophages, with greatest production observed following CI 79 and 86 challenge. Subsequently, C57BL/6 mice were challenged intraperitoneally with CI 77 and 79 to assess the role of PTX3 in vivo. A. baumannii strain CI 79 exhibited significantly (P < 0.0005) increased mortality, with an approximate 50% lethal dose (LD50) of 10(5) CFU, while an equivalent dose of CI 77 exhibited no mortality. Plasma leukocyte chemokines (KC, MCP-1, and RANTES) and myeloperoxidase activity were also significantly elevated following challenge with CI 79, indicating neutrophil recruitment/activation associated with significant elevation in serum PTX3 levels. Furthermore, 10-fold-greater PTX3 levels were observed in mouse serum 12 h postchallenge, comparing CI 79 to CI 77 (1,561 ng/ml versus 145 ng/ml), with concomitant severe pathology (liver and spleen) and coagulopathy. Together, these results suggest that elevation of PTX3 is associated with fulminant disease during A. baumannii sepsis.
authors.affiliation: University of Texas at San Antonio, San Antonio, Texas, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Ketter
authors.affiliation: University of Texas at San Antonio, San Antonio, Texas, USA.
authors.forename: M Neal
authors.initials: MN
authors.lastname: Guentzel
authors.affiliation: United States Army Institute for Surgical Research, San Antonio Military Medical Center, San Antonio, Texas, USA.
authors.forename: Beverly
authors.initials: B
authors.lastname: Schaffer
authors.affiliation: United States Army Institute for Surgical Research, San Antonio Military Medical Center, San Antonio, Texas, USA.
authors.forename: Maryanne
authors.initials: M
authors.lastname: Herzig
authors.affiliation: United States Army Institute for Surgical Research, San Antonio Military Medical Center, San Antonio, Texas, USA.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Wu
authors.affiliation: United States Army Institute for Surgical Research, San Antonio Military Medical Center, San Antonio, Texas, USA.
authors.forename: Robbie K
authors.initials: RK
authors.lastname: Montgomery
authors.affiliation: United States Army Institute for Surgical Research, San Antonio Military Medical Center, San Antonio, Texas, USA.
authors.forename: Bijaya K
authors.initials: BK
authors.lastname: Parida
authors.affiliation: United States Army Institute for Surgical Research, San Antonio Military Medical Center, San Antonio, Texas, USA.
authors.forename: Chriselda G
authors.initials: CG
authors.lastname: Fedyk
authors.affiliation: University of Texas at San Antonio, San Antonio, Texas, USA.
authors.forename: Jieh-Juen
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: James
authors.initials: J
authors.lastname: Jorgensen
authors.affiliation: University of Texas at San Antonio, San Antonio, Texas, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Chambers
authors.affiliation: United States Army Institute for Surgical Research, San Antonio Military Medical Center, San Antonio, Texas, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Cap
authors.affiliation: University of Texas at San Antonio, San Antonio, Texas, USA bernard.arulanandam@utsa.edu.
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
mesh_terms: D000151:Acinetobacter Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000276:immunology*; D000818:Animals; D002097:C-Reactive Protein / Q000276:immunology*; D002460:Cell Line; D018925:Chemokines / Q000097:blood; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D009419:Nerve Tissue Proteins / Q000097:blood / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D009195:Peroxidase / Q000097:blood; D018805:Sepsis / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D012772:Shock, Septic / Q000097:blood / Q000276:immunology* / Q000401:mortality; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D018925:Chemokines; D009419:Nerve Tissue Proteins; D009195:Peroxidase; D000099153:Pentraxins