Research Topics
Genomes and Genes | Christopher C SillimanSummaryAffiliation: University of Colorado Health Sciences Center Country: USA Publications
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Publications
Transfusion of the injured patient: proceed with cautionChristopher C Silliman
Bonfils Blood Center, Denver Health Medical Center, Denver, Colorado 80230, USA
Shock 21:291-9. 2004..We further summarize studies with hemoglobin substitutes, whose use may obviate many of the untoward events of transfusion and promise to lead to better outcomes for injured patients...- Lysophosphatidylcholines prime the NADPH oxidase and stimulate multiple neutrophil functions through changes in cytosolic calciumChristopher C Silliman
Bonfils Blood Center, Denver, Colorado 80230, USA
J Leukoc Biol 73:511-24. 2003..In conclusion, lyso-PCs affect multiple PMN functions in a Ca(2)(+)-dependent manner that involves the activation of a pertussis toxin-sensitive G-protein... 
Platelet-activating factor-mediated endosome formation causes membrane translocation of p67phox and p40phox that requires recruitment and activation of p38 MAPK, Rab5a, and phosphatidylinositol 3-kinase in human neutrophilsNathan J D McLaughlin
Bonfils Blood Center, University of Colorado Denver School of Medicine, Children s Hospital, Denver, CO 80230, USA
J Immunol 180:8192-203. 2008..In conclusion, PAF transduces signals through CME, and such GPCR signaling may allow for pharmacological manipulation of these cells to decrease PMN-mediated acute organ injury...- Platelet-activating factor-induced clathrin-mediated endocytosis requires beta-arrestin-1 recruitment and activation of the p38 MAPK signalosome at the plasma membrane for actin bundle formationNathan J D McLaughlin
Department of Pediatrics, University of Colorado School of Medicine, Denver, CO 80262, USA
J Immunol 176:7039-50. 2006..We conclude that PAF signaling requires CME, beta-arrestin-1 recruitment of a p38 MAPK signalosome, and specific actin bundle formation at the PAFR for transduction before endosomal scission... - Tumor necrosis factor-alpha causes release of cytosolic interleukin-18 from human neutrophilsChristopher C Silliman
Research Dept, Bonfils Blood Center, 717 Yosemite St, Denver, CO 80230, USA
Am J Physiol Cell Physiol 298:C714-24. 2010..Extracellular IL-18 participates in TNF-alpha priming of the PMN oxidase as demonstrated by inhibition with the IL-18 binding protein... - Formyl-Met-Leu-Phe induces calcium-dependent tyrosine phosphorylation of Rel-1 in neutrophilsMarguerite R Kelher
Department of Surgery, University of Colorado Health Science Center School of Medicine, Denver, CO 80230, USA
Cell Calcium 34:445-55. 2003..Thus, fMLP concentrations that prime or activate the oxidase cause a rapid Ca2+-dependent tyrosine phosphorylation of Rel-1 involving p38 MAPK activation... - Lysophosphatidylcholines activate G2A inducing G(αi)₋₁-/G(αq/)₁₁- Ca²(+) flux, G(βγ)-Hck activation and clathrin/β-arrestin-1/GRK6 recruitment in PMNsSamina Y Khan
Bonfils Blood Center, Denver, CO 80230, USA
Biochem J 432:35-45. 2010..We conclude that lyso-PC activation of G2A caused release of G(αi)₋₁, G(αq/)₁₁ and G(βγ), resulting in cytosolic Ca²(+) flux, Hck activation, and recruitment of clathrin, β-arrestin-1 and GRK6... - Amantadine inhibits platelet-activating factor induced clathrin-mediated endocytosis in human neutrophilsPhillip C Eckels
Department of Surgery, Denver Health Medical Center, Denver, Colorado, USA
Am J Physiol Cell Physiol 297:C886-97. 2009..Thus, amantadine and rimantadine have the potential to ameliorate PMN-mediated tissue damage in humans... 
Accumulation of pro-cancer cytokines in the plasma fraction of stored packed red cellsDouglas D Benson
Denver Health Medical Center, 777 Bannock St, Denver, CO 80204 0206, USA
J Gastrointest Surg 16:460-8. 2012..We analyzed the plasma fraction of stored pRBCs for pro-cancer cytokines and evaluated the affect of both storage time and leukocyte reduction on these mediators...- Arachidonic acid in postshock mesenteric lymph induces pulmonary synthesis of leukotriene B4Janeen R Jordan
Department of Surgery, University of Colorado Denver, Denver, CO, USA
J Appl Physiol 104:1161-6. 2008..Collectively, these data indicate that splanchnic ischemia/reperfusion activates gut PLA(2)-mediated release of AA into the lymph where it is delivered to the lungs, provoking LTB(4) production and subsequent PMN-mediated lung injury... - Activation state of stromal inflammatory cells in murine metastatic pancreatic adenocarcinomaDouglas D Benson
Denver Health Medical Center, Denver, CO 80204 0206, USA
Am J Physiol Regul Integr Comp Physiol 302:R1067-75. 2012..TANs are localized at the invasive front of the metastasis, where they colocalize with MMP-9. Improved understanding of these interactions may lead to targeted therapies for pancreas adenocarcinoma... - Identification of lipids that accumulate during the routine storage of prestorage leukoreduced red blood cells and cause acute lung injuryChristopher C Silliman
Bonfils Blood Center, and the Department of Surgery, Denver Health Medical, Denver, Colorado 80230, USA
Transfusion 51:2549-54. 2011.... - Plasma from stored packed red blood cells and MHC class I antibodies causes acute lung injury in a 2-event in vivo rat modelMarguerite R Kelher
Bonfils Blood Center, Denver, CO 80230, USA
Blood 113:2079-87. 2009..We conclude that TRALI is the result of 2 events with the second events consisting of the plasma from stored blood and antibodies that prime PMNs... - Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activationForest R Sheppard
Department of Surgery, Denver Health Medical Center, Colorado, USA
J Leukoc Biol 78:1025-42. 2005..This review will discuss the individual components associated with the NADPH oxidase complex and the function of each of these units in each physiologic stage of the PMN: rested, primed, and activated... - Leukotriene b4 and its metabolites prime the neutrophil oxidase and induce proinflammatory activation of human pulmonary microvascular endothelial cellsJohn C Eun
The Department of Surgery, Denver Health Medical Center, Colorado, USA
Shock 35:240-4. 2011..These data have expanded the repertoire of causative agents in acute lung injury and postinjury multiple organ failure... - Presence of the M-type sPLA(2) receptor on neutrophils and its role in elastase release and adhesionChristopher C Silliman
Bonfils Blood Center, Department of Pediatrics, University of Colorado School of Medicine, Denver, CO 80262, USA
Am J Physiol Cell Physiol 283:C1102-13. 2002..sPLA(2)-IB and sPLA(2)-IIA caused PMN adhesion. We conclude that PMNs contain a membrane M-type sPLA(2)-R that activates p38 MAPK... - Red blood cell supernatant potentiates LPS-induced proinflammatory cytokine response from peripheral blood mononuclear cellsJoel M Baumgartner
Department of Surgery, University of Colorado, Denver, Aurora, CO 80045, USA
J Interferon Cytokine Res 29:333-8. 2009..This response is accentuated with storage duration and partially attenuated with leukoreduction. These findings may partially explain the immune activation seen clinically after blood transfusion... - Alteration of the postinjury hyperinflammatory response by means of resuscitation with a red cell substituteJeffrey L Johnson
Department of Surgery, Denver Health Medical Center, 777 Bannock Street, Denver, CO 80204, USA
J Trauma 54:133-9; discussion 139-40. 2003..Through the use of a polymerized human hemoglobin (PolyHeme), we have been able to measure the inflammatory response in patients resuscitated with minimal exposure to banked components in the early postinjury period... - A two-insult in vitro model of PMN-mediated pulmonary endothelial damage: requirements for adherence and chemokine releaseTravis H Wyman
Bonfils Blood Center and Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado 80230, USA
Am J Physiol Cell Physiol 283:C1592-603. 2002..In conclusion, sequential exposure of PMNs to priming agents activates the microbicidal arsenal, and PMN-mediated HMVEC damage was the result of two insults: HMVEC activation and PMN oxidase assembly... - Clinically relevant osmolar stress inhibits priming-induced PMN NADPH oxidase subunit translocationForest R Sheppard
Department of Surgery, Denver Health Medical Center, University of Colorado School of Medicine, Denver, Colorado, USA
J Trauma 58:752-7; discussion 757. 2005..This finding provides new insight into the mechanisms responsible for osmolar control of PMN functional responses... - Hemodilution is not critical in the pathogenesis of the acute coagulopathy of traumaMax Valentin Wohlauer
Department of Surgery, University of Colorado Denver, Denver, Colorado, USA
J Surg Res 173:26-30. 2012..We therefore hypothesized that hemodilution will impair coagulation following experimental trauma and hemorrhagic shock... - The plasma fraction of stored erythrocytes augments pancreatic cancer metastasis in male versus female micePeter K Moore
School of Medicine, University of Colorado at Denver, Denver, Colorado, USA
J Surg Res 164:23-7. 2010..We therefore hypothesize that male mice with pancreatic cancer will have greater tumor progression than female mice in response to transfusion... - Systemic neutrophil priming by lipid mediators in post-shock mesenteric lymph exists across speciesEric L Sarin
Departments of Surgery, Denver Health Medical Center and University of Colorado Health Sciences Center, Denver, Colorado 80204, USA
J Trauma 57:950-4. 2004..Further, the causal agent(s) exist in the lipid fraction of the lymph and are active on both human and animal PMNs... - Cross-transfusion of postshock mesenteric lymph provokes acute lung injuryMax Valentin Wohlauer
Department of Surgery, University of Colorado Denver, Denver, Colorado, USA
J Surg Res 170:314-8. 2011..However, Koch's postulates remain to be satisfied via direct cross-transfusion into a naïve animal. We therefore hypothesized that real time cross-transfusion of postshock mesenteric lymph provokes acute lung injury... - Early platelet dysfunction: an unrecognized role in the acute coagulopathy of traumaMax V Wohlauer
Department of Surgery, University of Colorado Denver, Denver, CO, USA
J Am Coll Surg 214:739-46. 2012..Although the current debate on acute traumatic coagulopathy has focused on the consumption or inhibition of coagulation factors, the question of early platelet dysfunction in this setting remains unclear... - Proteomic analyses of human plasma: Venus versus MarsChristopher C Silliman
Bonfils Blood Center, Denver, Colorado 80230, USA
Transfusion 52:417-24. 2012..Little is known about the human plasma proteome, and no comparisons have been made between male and female plasma; therefore, we hypothesize that there are significant differences between plasma from male and female donors... - A two-event in vitro model of acute chest syndrome: the role of secretory phospholipase A2 and neutrophilsJ Bradley Ball
The Research Department, Bonfils Blood Center, 717 Yosemite Street, Denver, CO 80230, USA
Pediatr Blood Cancer 58:399-405. 2012..We hypothesize that sPLA(2) cleaves membrane lipids from sickled red blood cells (RBCs) causing PMN-mediated endothelial cell injury (ECI) as the second event in a two-event model... - Transfusion-induced leukocyte IL-8 gene expression is avoided by the use of human polymerized hemoglobinForest R Sheppard
Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado 80204, USA
J Trauma 57:720-4; discussion 724-5. 2004..These experimental results corroborate our previous clinical studies and further encourage the study of PolyHb as a resuscitation strategy to decrease postinjury MOF... - Soluble CD40 ligand accumulates in stored blood components, primes neutrophils through CD40, and is a potential cofactor in the development of transfusion-related acute lung injurySamina Yasmin Khan
Bonfils Blood Center, 717 Yosemite St, Denver, CO 80230, USA
Blood 108:2455-62. 2006..We concluded that sCD40L, which accumulates during blood component storage, has the capacity to activate adherent PMNs, causing endothelial damage and possibly TRALI in predisposed patients... - Intravenous delivery of the plasma fraction of stored packed erythrocytes promotes pancreatic cancer growth in immunocompetent miceCarlton C Barnett
Department of Surgery, University of Colorado at Denver, Denver Health Medical Center, Denver, Colorado 80204 0206, USA
Cancer 116:3862-74. 2010.... - Therapeutic options for transfusion related acute lung injury; the potential of the G2A receptorMichael A Ellison
Belle Bonfils Memorial Blood Center, Denver, CO 80230, USA
Curr Pharm Des 18:3255-9. 2012..Additionally, characterization of the process by which lyso-PCs are generated in stored blood products could allow development of inhibitors and additive solutions to block their formation in the first place... - Activated platelets in heparinized shed blood: the "second hit" of acute lung injury in trauma/hemorrhagic shock modelsJeffrey N Harr
Department of Surgery, University of Colorado Denver, Denver, Colorado, USA
Shock 36:595-603. 2011..0001). The return of heparinized SB functions as a "second hit" to enhance ALI, with activated platelets propagating microthrombi and pulmonary polymorphonuclear leukocyte recruitment... - Viscoelastic clot strength predicts coagulation-related mortality within 15 minutesMichael Pezold
Department of Surgery, University of Colorado at Denver, Denver, CO, USA
Surgery 151:48-54. 2012..We hypothesized that clot strength (G) measured by point-of-care rapid thrombelastography (r-TEG) on arrival in the emergency department can predict massive transfusion (MT) and coagulation-related mortality (MT-death)... - Plasma and lipids from stored platelets cause acute lung injury in an animal modelChristopher C Silliman
Bonfils Blood Center, 717 Yosemite Circle, Denver, CO 80123, USA
Transfusion 43:633-40. 2003..We hypothesize that lipids generated during storage of PLTs cause TRALI in a two-event animal model... - Increased rate of infection associated with transfusion of old blood after severe injuryPatrick J Offner
Trauma Service, St Anthony Central Hospital, 4231 W 16th Ave, Denver, CO 80204, USA
Arch Surg 137:711-6; discussion 716-7. 2002..We hypothesized that transfusion of old blood increases infection risk in severely injured patients... - The role of endothelial activation in the pathogenesis of transfusion-related acute lung injuryChristopher C Silliman
Bonfils Blood Center and the Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado 80230, USA
Transfusion 45:109S-116S. 2005 - "Primed" human neutrophils on a standard peripheral blood smearorest R Sheppard
University of Colorado Health Sciences Center, Denver, USA
J Am Coll Surg 195:731. 2002 - The two-event model of transfusion-related acute lung injuryChristopher C Silliman
Bonfils Blood Center and Departments of Pediatrics and Surgery, University of Colorado School of Medicine, Denver, CO, USA
Crit Care Med 34:S124-31. 2006..Laboratory studies, both in vitro and in vivo, are discussed as well as human studies of TRALI. Methods to avoid patient exposure to blood components that may cause TRALI are also discussed... - Transfusion-related acute lung injuryChristopher C Silliman
Bonfils Blood Center, 717 Yosemite St, Denver, CO 80230, USA
Blood 105:2266-73. 2005..Prevention, treatment, and a proposed definition of TRALI, especially in the context of ALI, are also examined... - Functional fibrinogen assay indicates that fibrinogen is critical in correcting abnormal clot strength following traumaJeffrey N Harr
Department of Surgery, University of Colorado Denver, Aurora, CO, USA
Shock 39:45-9. 2013..These data suggest that fibrinogen should be addressed early in trauma patients manifesting acute coagulopathy of trauma... - Gender-specific transfusion affects tumor-associated neutrophil: macrophage ratios in murine pancreatic adenocarcinomaDouglas D Benson
Denver Health Medical Center, 777 Bannock Street, Denver, CO 80204 0206, USA
J Gastrointest Surg 14:1560-5. 2010..To test this hypothesis, we examined tumor-associated neutrophils and macrophage ratios in male and female mice with pancreatic cancer receiving blood transfusion from male or female donors... - Hyperosmolarity abrogates neutrophil cytotoxicity provoked by post-shock mesenteric lymphRicardo J Gonzalez
Denver Health Medical Center, Department of Surgery, Colorado 80204, USA
Shock 18:29-32. 2002..These studies suggest inhibition of PMN signal transduction is a mechanism whereby HTS resuscitation abrogates acute lung injury... - Stored red blood cell transfusion induces regulatory T cellsJoel M Baumgartner
Department of Surgery, University of Colorado Denver, Denver, CO, USA
J Am Coll Surg 208:110-9. 2009..We hypothesized that transfusion-related immunosuppression is, in part, mediated by induction of T(regs), and this induction is attenuated with prestorage leukoreduction and accentuated with prolonged storage... - Transfusion-related acute lung injury (TRALI): current concepts and misconceptionsChristopher C Silliman
Research Department, Bonfils Blood Center, Denver CO 80230, USA
Blood Rev 23:245-55. 2009..This review will detail the pathophysiology of TRALI including recent pre-clinical data, provide insight into newer areas of research, and critically assess current practices to decrease it prevalence and to make transfusion safer... - Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factorsChristopher C Silliman
Bonfils Blood Center and the Department of Pediatrics, University of Colorado School of Medicine, Denver, USA
Blood 101:454-62. 2003..TRALI, like the acute respiratory distress syndrome, may be a 2-event phenomenon with both recipient predisposition and factors in the stored units playing major roles... - Transfusion-related acute lung injuryChristopher C Silliman
Bonfils Blood Center, University of Colorado School of Medicine, 717 Yosemite Circle, Denver, CO 80230, USA
Blood Rev 20:139-59. 2006..The definition of TRALI, patient predisposition, treatment, prevention and reporting guidelines are also examined... - Biological response modifiers in photochemically pathogen-reduced versus untreated apheresis platelet concentratesAnnette Vetlesen
Department of Immunology and Transfusion Medicine, Oslo University Hospital, Ullevaal, Oslo, Norway
Transfusion 53:147-55. 2013..This study compared the content and impact of some biological response modifiers in PCs treated with pathogen reduction (PR) technology and nontreated PCs... - Sexual dimorphism in hematocrit response following red blood cell transfusion of critically ill surgical patientsFredric M Pieracci
Department of Surgery, Denver Health Medical Center, University of Colorado Health Science Center, 777 Bannock Street MC0206, Denver, CO 80206, USA
ISRN Hematol 2012:298345. 2012..This association does not appear related to either demographic or anthropomorphic factors, raising the possibility of gender-related differences in recipient immune response to transfusion... - Acute hypoxemia in humans enhances the neutrophil inflammatory responseDouglas Y Tamura
Department of Surgery, Denver Health Medical Center, Colorado, USA
Shock 17:269-73. 2002..These results indicate that relevant acute hypoxemic events observed in the clinical setting enhance several PMN cytotoxic functions and suggest that a transient hypoxemic insult may promote hyperinflammation... - Physiological levels of interleukin-18 stimulate multiple neutrophil functions through p38 MAP kinase activationTravis H Wyman
Bonfils Blood Center, Denver, CO 80230, USA
J Leukoc Biol 72:401-9. 2002..We conclude that IL-18, at physiologic concentrations, is an effective PMN priming agent that requires p38 MAP kinase activity... - Differentiation of enzymatic from platelet hypercoagulability using the novel thrombelastography parameter delta (delta)Eduardo Gonzalez
Department of Surgery, Denver Health Medical Center and University of Colorado School of Medicine, Denver, Colorado, USA
J Surg Res 163:96-101. 2010..Delta).. - The abdominal compartment syndrome as a second insult during systemic neutrophil priming provokes multiple organ injuryJoao B Rezende-Neto
Department of Surgery, Faculty of Medicine of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil 30350-210
Shock 20:303-8. 2003..This clinically relevant two-event animal model of PMN organ injury may be useful in elucidating therapy strategies to prevent postinjury MOF... - The transfusion of pre storage leukoreduced packed red blood cells to injured patientsChristopher C Silliman
Crit Care Med 36:1661-2. 2008 - The injured child is resistant to multiple organ failure: a different inflammatory response?Casey M Calkins
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA
J Trauma 53:1058-63. 2002..The purpose of this study was to describe the incidence, course, and severity of pediatric postinjury MOF. We hypothesized that the incidence and severity of postinjury MOF in children would be less when compared with adults... - Post-hemorrhagic shock mesenteric lymph activates human pulmonary microvascular endothelium for in vitro neutrophil-mediated injury: the role of intercellular adhesion molecule-1Ricardo J Gonzalez
Department of Surgery, Denver Health Medical Center and University of Colorado, 80204, USA
J Trauma 54:219-23. 2003..These findings further substantiate the key mechanistic role of mesenteric lymph in hemorrhagic shock-induced acute lung injury and suggest that ICAM-1 expression is pivotal in the two-event model of multiple organ failure... - Clinically relevant hypertonicity prevents stored blood- and lipid-mediated delayed neutrophil apoptosis independent of p38 MAPK or caspase-3 activationWalter L Biffl
Department of Surgery, Rhode Island Hospital/Brown Medical School, Providence, RI, USA
Surgery 134:86-91. 2003..HTS may activate caspase-3, but alternative signaling pathways appear to be involved in modulating the effects of lipids on PMN apoptosis...