Home LiteratureArticle Details
PMID: 17143330 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation.

The Journal of clinical investigation ·Vol. 116 ·No. 12 ·2006-12-00 ·Pages 3211-9

Zarbock A, Singbartl K, Ley K

Abstract

Acute lung injury (ALI) causes high mortality, but its molecular mechanisms are poorly understood. Acid aspiration is a frequent cause of ALI, leading to neutrophil sequestration, increased permeability, and deterioration of gas exchange. We investigated the role of platelet-neutrophil interactions in a murine model of acid-induced ALI. Acid aspiration induced P-selectin-dependent platelet-neutrophil interactions in blood and in lung capillaries. Reducing circulating platelets or blocking P-selectin halted the development of ALI. Bone marrow chimeras showed that platelet, not endothelial, P-selectin was responsible for the injury. The interaction of platelets with neutrophils and endothelia was associated with TXA(2) formation, with detrimental effects on permeability and tissue function. Activated platelets induced endothelial expression of ICAM-1 and increased neutrophil adhesion. Inhibition of platelet-neutrophil aggregation improved gas exchange, reduced neutrophil recruitment and permeability, and prolonged survival. The key findings were confirmed in a sepsis-induced model of ALI. These findings may translate into improved clinical treatments for ALI.

MeSH Terms
Acids/toxicity Animals Blood Platelets/cytology,drug effects Busulfan/pharmacology Cell Adhesion/drug effects Cell Communication/drug effects Cells, Cultured Disease Models, Animal Endothelial Cells/cytology,drug effects,metabolism Flow Cytometry Humans Lung/drug effects,metabolism,pathology Mice Mice, Inbred C57BL Neutrophil Activation/drug effects Neutrophils/cytology,drug effects,metabolism P-Selectin/metabolism,physiology Platelet Activation/drug effects Platelet Aggregation/drug effects Receptors, Thromboxane/antagonists & inhibitors Respiratory Distress Syndrome/chemically induced,metabolism,prevention & control
Chemicals
Acids P-Selectin Receptors, Thromboxane Busulfan
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zarbock Alexander
Robert M Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908-1394, USA.
Singbartl Kai
Ley Klaus
References (50)
50 references, click to expand
  1. A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process.
    Blood. 1998 Apr 15;91(8):3028-36 PMID: 9531616
  2. Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome.
    JAMA. 2003 Apr 23-30;289(16):2104-12 PMID: 12709468
  3. The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin.
    J Exp Med. 1999 Sep 20;190(6):803-14 PMID: 10499919
  4. Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation.
    Blood. 2005 Mar 1;105(5):2074-81 PMID: 15528309
  5. Angiotensin-converting enzyme 2 protects from severe acute lung failure.
    Nature. 2005 Jul 7;436(7047):112-6 PMID: 16001071
  6. Sequential recruitment of neutrophils into lung and bronchoalveolar lavage fluid in LPS-induced acute lung injury.
    Am J Physiol Lung Cell Mol Physiol. 2005 Nov;289(5):L807-15 PMID: 15951336
  7. Incidence and outcomes of acute lung injury.
    N Engl J Med. 2005 Oct 20;353(16):1685-93 PMID: 16236739
  8. Low-dose aspirin for the prevention of atherothrombosis.
    N Engl J Med. 2005 Dec 1;353(22):2373-83 PMID: 16319386
  9. Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia--a review.
    Crit Care Med. 2006 Mar;34(3):871-7 PMID: 16521285
  10. The beta-thromboglobulins and platelet factor 4: blood platelet-derived CXC chemokines with divergent roles in early neutrophil regulation.
    J Leukoc Biol. 2000 Apr;67(4):471-8 PMID: 10770278
  11. The acute respiratory distress syndrome.
    N Engl J Med. 2000 May 4;342(18):1334-49 PMID: 10793167
  12. Obligatory role of lipid mediators in platelet-neutrophil adhesion.
    Thromb Res. 2003 Jun 15;110(5-6):287-92 PMID: 14592550
  13. Cell signalling through thromboxane A2 receptors.
    Cell Signal. 2004 May;16(5):521-33 PMID: 14751539
  14. Adult respiratory distress syndrome: risk with common predispositions.
    Ann Intern Med. 1983 May;98(5 Pt 1):593-7 PMID: 6846973
  15. Aspiration during anaesthesia: a computer-aided study of 185,358 anaesthetics.
    Acta Anaesthesiol Scand. 1986 Jan;30(1):84-92 PMID: 3754372
  16. GMP-140 mediates adhesion of stimulated platelets to neutrophils.
    Blood. 1990 Feb 1;75(3):550-4 PMID: 1688717
  17. Neutrophil accumulations due to pulmonary thromboxane synthesis mediate acid aspiration injury.
    J Appl Physiol (1985). 1991 Apr;70(4):1511-7 PMID: 2055829
  18. Activated and unactivated platelet adhesion to monocytes and neutrophils.
    Blood. 1991 Oct 1;78(7):1760-9 PMID: 1717070
  19. Thromboxane-induced neutrophil adhesion to pulmonary microvascular and aortic endothelium is regulated by CD18.
    Inflammation. 1991 Jun;15(3):181-99 PMID: 1682250
  20. Synergism between leukotriene B4 and thromboxane A2 in mediating acid-aspiration injury.
    Surgery. 1992 Jan;111(1):55-61 PMID: 1309402
  21. Reactive oxygen species and elastase mediate lung permeability after acid aspiration.
    J Appl Physiol (1985). 1992 Aug;73(2):571-5 PMID: 1399982
  22. Clinical significance of pulmonary aspiration during the perioperative period.
    Anesthesiology. 1993 Jan;78(1):56-62 PMID: 8424572
  23. Surfactant treatment of respiratory failure induced by hydrochloric acid aspiration in rats.
    Anesthesiology. 1993 Jun;78(6):1145-51 PMID: 8512108
  24. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines.
    Adv Immunol. 1994;55:97-179 PMID: 8304236
  25. Clinical risks for development of the acute respiratory distress syndrome.
    Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):293-301 PMID: 7842182
  26. Polymorphonuclear leukocyte-platelet interaction: role of P-selectin in thromboxane B2 and leukotriene C4 cooperative synthesis.
    Thromb Haemost. 1994 Sep;72(3):450-6 PMID: 7531878
  27. Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion. Signal integration and NF-kappa B translocation.
    J Clin Invest. 1995 May;95(5):2297-303 PMID: 7537762
  28. Intercellular adhesion molecule-1 mediates acid aspiration-induced lung injury.
    Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):504-10 PMID: 8756829
  29. Postinjury thromboxane receptor blockade ameliorates acute lung injury.
    Ann Thorac Surg. 1997 Sep;64(3):826-9 PMID: 9307481
  30. Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor.
    J Clin Invest. 1997 Oct 15;100(8):2085-93 PMID: 9329974
  31. Engagement of P-selectin glycoprotein ligand-1 enhances tyrosine phosphorylation and activates mitogen-activated protein kinases in human neutrophils.
    J Biol Chem. 1997 Nov 7;272(45):28750-6 PMID: 9353345
  32. Adhesion of activated platelets to endothelial cells: evidence for a GPIIbIIIa-dependent bridging mechanism and novel roles for endothelial intercellular adhesion molecule 1 (ICAM-1), alphavbeta3 integrin, and GPIbalpha.
    J Exp Med. 1998 Feb 2;187(3):329-39 PMID: 9449713
  33. Platelet-endothelial interactions in inflamed mesenteric venules.
    Blood. 1998 Feb 15;91(4):1318-24 PMID: 9454762
  34. Stimulation of P-selectin glycoprotein ligand-1 on mouse neutrophils activates beta 2-integrin mediated cell attachment to ICAM-1.
    Eur J Immunol. 1998 Feb;28(2):433-43 PMID: 9521050
  35. Modulation of human neutrophil apoptosis by immune complexes.
    J Immunol. 1998 Oct 1;161(7):3666-74 PMID: 9759891
  36. Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. The ARDS Network.
    JAMA. 2000 Apr 19;283(15):1995-2002 PMID: 10789668
  37. Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins.
    Blood. 2000 Nov 15;96(10):3322-8 PMID: 11071623
  38. A role for platelets and endothelial selectins in tumor necrosis factor-alpha-induced leukocyte recruitment in the brain microvasculature.
    Circ Res. 2000 Dec 8;87(12):1141-8 PMID: 11110771
  39. Platelet-derived CXC chemokines: old players in new games.
    Immunol Rev. 2000 Oct;177:204-16 PMID: 11138777
  40. Aspiration pneumonitis and aspiration pneumonia.
    N Engl J Med. 2001 Mar 1;344(9):665-71 PMID: 11228282
  41. Mouse carotid artery ligation induces platelet-leukocyte-dependent luminal fibrin, required for neointima development.
    Circ Res. 2001 Feb 2;88(2):159-66 PMID: 11157667
  42. Specific reverse transcription-PCR quantification of vascular endothelial growth factor (VEGF) splice variants by LightCycler technology.
    Clin Chem. 2001 Apr;47(4):654-60 PMID: 11274014
  43. Acute lung injury by sepsis and acid aspiration: a key role for cytosolic phospholipase A2.
    Nat Immunol. 2000 Jul;1(1):42-6 PMID: 10881173
  44. Mechanisms of leukocyte sequestration in inflamed lungs.
    Microcirculation. 2001 Apr;8(2):71-88 PMID: 11379793
  45. Increased granulopoiesis through interleukin-17 and granulocyte colony-stimulating factor in leukocyte adhesion molecule-deficient mice.
    Blood. 2001 Dec 1;98(12):3309-14 PMID: 11719368
  46. The complexities of leukocyte recruitment.
    Semin Immunol. 2002 Apr;14(2):65-72 PMID: 11978078
  47. A new mathematical model for relative quantification in real-time RT-PCR.
    Nucleic Acids Res. 2001 May 1;29(9):e45 PMID: 11328886
  48. Platelets in atherothrombosis.
    Nat Med. 2002 Nov;8(11):1227-34 PMID: 12411949
  49. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E.
    Nat Med. 2003 Jan;9(1):61-7 PMID: 12483207
  50. Thromboxane synthesis is increased by upregulation of cytosolic phospholipase A2 and cyclooxygenase-2 in peripheral polymorphonuclear leukocytes during bacterial infection in childhood.
    Am J Hematol. 2003 Feb;72(2):115-20 PMID: 12555215
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI29499
Published
2006-12-00
Pages
3211-9
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1679711
Subset
IM
Grants
NHLBI NIH HHS · P01 HL073361 · United States
NHLBI NIH HHS · P01 HL 73361 · United States
Corrections
CommentIn
PMID: 17143325
External Links
PubMed source DOI: 10.1172/JCI29499 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2