A genomic storm in critically injured humans

被引：818

作者：

Xiao, Wenzhong ^{[1
,4
]}

Mindrinos, Michael N. ^{[4
]}

Seok, Junhee ^{[4
]}

Cuschieri, Joseph ^{[6
]}

Cuenca, Alex G. ^{[5
]}

Gao, Hong ^{[4
]}

Hayden, Douglas L. ^{[2
]}

Hennessy, Laura ^{[6
]}

Moore, Ernest E. ^{[7
]}

Minei, Joseph P. ^{[8
]}

Bankey, Paul E. ^{[9
]}

Johnson, Jeffrey L. ^{[7
]}

Sperry, Jason

Nathens, Avery B. ^{[11
]}

Billiar, Timothy R. ^{[10
]}

West, Michael A. ^{[12
]}

Brownstein, Bernard H. ^{[13
]}

Mason, Philip H. ^{[1
]}

Baker, Henry V. ^{[5
]}

Finnerty, Celeste C. ^{[14
]}

Jeschke, Marc G. ^{[15
]}

Lopez, M. Cecilia ^{[5
]}

Klein, Matthew B. ^{[6
]}

Gamelli, Richard L. ^{[16
]}

Gibran, Nicole S. ^{[6
]}

Arnoldo, Brett ^{[8
]}

Xu, Weihong ^{[4
]}

Zhang, Yuping ^{[4
]}

Calvano, Steven E. ^{[17
]}

McDonald-Smith, Grace P. ^{[1
]}

Schoenfeld, David A. ^{[2
]}

Storey, John D. ^{[18
]}

Cobb, J. Perren ^{[3
]}

Warren, H. Shaw ^{[2
]}

Moldawer, Lyle L. ^{[5
]}

Herndon, David N. ^{[14
]}

Lowry, Stephen F. ^{[17
]}

Maier, Ronald V. ^{[6
]}

Davis, Ronald W. ^{[4
]}

Tompkins, Ronald G. ^{[1
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA

[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA

[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care Med & Pain Med, Boston, MA 02114 USA

[4] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA

[5] Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA

[6] Univ Washington, Sch Med, Dept Surg, Harborview Med Ctr, Seattle, WA 98104 USA

[7] Univ Colorado, Dept Surg, Denver, CO 80045 USA

[8] Univ Texas SW Med Ctr Dallas, Dept Surg, Parkland Mem Hosp, Dallas, TX 75390 USA

[9] Univ Rochester, Dept Surg, Med Ctr, Rochester, NY 14642 USA

[10] Univ Pittsburgh, Dept Surg, Presbyterian Med Ctr, Univ Hosp, Pittsburgh, PA 15213 USA

[11] St Michaels Hosp, Dept Surg, Toronto, ON M5B 1W8, Canada

[12] Univ Calif San Francisco, Dept Surg, San Francisco Gen Hosp, San Francisco, CA 94110 USA

[13] Washington Univ, Dept Surg, Sch Med St Louis, St Louis, MO 63110 USA

[14] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA

[15] Univ Toronto, Dept Surg, Div Plast & Reconstruct Surg, Toronto, ON M5G 1L5, Canada

[16] Loyola Univ, Dept Surg, Stritch Sch Med, Maywood, IL 60153 USA

[17] Univ Med & Dent New Jersey, Dept Surg, Robert Wood Johnson Med Sch, New Brunswick, NJ 08901 USA

[18] Princeton Univ, Dept Mol Biol, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2011年 / 208卷 / 13期

关键词：

SCALE COLLABORATIVE PROJECT; ORIENTED RESEARCH CORE; STANDARD OPERATING PROCEDURES; MULTIPLE ORGAN FAILURE; CLINICAL CARE; HOST RESPONSE; TRAUMA PATIENT; GENE-EXPRESSION; IMMUNE-SYSTEM; INFLAMMATION;

D O I：

10.1084/jem.20111354

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected "genomic storm." In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.

引用

页码：2581 / 2590

页数：10

共 41 条

[1] Gene expression during the life cycle of Drosophila melanogaster [J].

Arbeitman, MN ;

Furlong, EEM ;

Imam, F ;

Johnson, E ;

Null, BH ;

Baker, BS ;

Krasnow, MA ;

Scott, MP ;

Davis, RW ;

White, KP .

SCIENCE, 2002, 297 (5590) :2270-2275

[2] Sensors of the innate immune system: their mode of action [J].

Baccala, Roberto ;

Gonzalez-Quintial, Rosana ;

Lawson, Brian R. ;

Stern, Michael E. ;

Kono, Dwight H. ;

Beutler, Bruce ;

Theofilopoulos, Argyrios N. .

NATURE REVIEWS RHEUMATOLOGY, 2009, 5 (08) :448-456

[3] Maumee: My Walden pond [J].

Bone, RC .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1996, 276 (24) :1931-1931

[4] Sir Isaac Newton, sepsis, SIRS, and CARS [J].

Bone, RC .

CRITICAL CARE MEDICINE, 1996, 24 (07) :1125-1128

[5] A network-based analysis of systemic inflammation in humans [J].

Calvano, SE ;

Xiao, WZ ;

Richards, DR ;

Felciano, RM ;

Baker, HV ;

Cho, RJ ;

Chen, RO ;

Brownstein, BH ;

Cobb, JP ;

Tschoeke, SK ;

Miller-Graziano, C ;

Moldawer, LL ;

Mindrinos, MN ;

Davis, RW ;

Tompkins, RG ;

Lowry, SF .

NATURE, 2005, 437 (7061) :1032-1037

[6] Inflammation and the Host Response to Injury a Large-Scale Collaborative Project: Patient-Oriented Research Core Standard Operating Procedure for Clinical Care X. Guidelines for Venous Thromboembolism Prophylaxis in the Trauma Patient [J].

Cuschieri, Joseph ;

Freeman, Brad ;

O'Keefe, Grant ;

Harbrecht, Brian G. ;

Bankey, Paul ;

Johnson, Jeffrey L. ;

Minei, Joseph P. ;

Sperry, Jason ;

West, Michael ;

Nathens, Avery ;

Moore, Ernest E. ;

Maier, Ronald V. .

JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE, 2008, 65 (04) :944-950

[7]

D'Agostino RB, 1998, STAT MED, V17, P2265, DOI 10.1002/(SICI)1097-0258(19981015)17:19<2265::AID-SIM918>3.0.CO

[8]

2-B

[9] Long-term Survival of Adult Trauma Patients [J].

Davidson, Giana H. ;

Hamlat, Christian A. ;

Rivara, Frederick P. ;

Koepsell, Thomas D. ;

Jurkovich, Gregory J. ;

Arbabi, Saman .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2011, 305 (10) :1001-1007

[10] Cytokines in patients with polytrauma [J].

DeLong, WG ;

Born, CT .

CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 2004, (422) :57-65

← 1 2 3 4 5 →