neutrophil activation


Summary: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cell-surface receptors on the neutrophil.

Top Publications

  1. Maugeri N, Rovere Querini P, Slavich M, Coppi G, Doni A, Bottazzi B, et al. Early and transient release of leukocyte pentraxin 3 during acute myocardial infarction. J Immunol. 2011;187:970-9 pubmed publisher
    ..PTX3 binds to activated circulating platelets and dampens their proinflammatory and prothrombotic action, thus possibly contributing to its cardioprotective effects. ..
  2. Yipp B, Kubes P. NETosis: how vital is it?. Blood. 2013;122:2784-94 pubmed publisher
    ..Finally, we examine how infections are related to the development of autoimmune and vasculitic diseases through unintended but detrimental bystander damage resulting from NET release. ..
  3. Keshari R, Jyoti A, Kumar S, Dubey M, Verma A, Srinag B, et al. Neutrophil extracellular traps contain mitochondrial as well as nuclear DNA and exhibit inflammatory potential. Cytometry A. 2012;81:238-47 pubmed publisher
    ..These NETs were made up of mitochondrial and nuclear DNA and potentiated release of proinflammatory cytokines. ..
  4. Thom S, Milovanova T, Bogush M, Bhopale V, Yang M, Bushmann K, et al. Microparticle production, neutrophil activation, and intravascular bubbles following open-water SCUBA diving. J Appl Physiol (1985). 2012;112:1268-78 pubmed publisher
    The goal of this study was to evaluate annexin V-positive microparticles (MPs) and neutrophil activation in humans following decompression from open-water SCUBA diving with the hypothesis that changes are related to intravascular bubble ..
  5. Pereira da Silva G, Carvalho F, Roque Barreira M. Neutrophil activation induced by plant lectins: modulation of inflammatory processes. Inflamm Allergy Drug Targets. 2012;11:433-41 pubmed
    ..The reports included herein illustrate the modulation of inflammatory processes by plant lectins. ..
  6. Maugeri N, Rovere Querini P, Evangelista V, Godino C, Demetrio M, Baldini M, et al. An intense and short-lasting burst of neutrophil activation differentiates early acute myocardial infarction from systemic inflammatory syndromes. PLoS ONE. 2012;7:e39484 pubmed publisher
    Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS) compared to stable angina and to systemic inflammatory diseases...
  7. Bertram A, Ley K. Protein kinase C isoforms in neutrophil adhesion and activation. Arch Immunol Ther Exp (Warsz). 2011;59:79-87 pubmed publisher
    ..This review focuses on the potential impact of protein kinase C isoforms on neutrophil adhesion and activation. ..
  8. Ramma W, Buhimschi I, Zhao G, Dulay A, Nayeri U, Buhimschi C, et al. The elevation in circulating anti-angiogenic factors is independent of markers of neutrophil activation in preeclampsia. Angiogenesis. 2012;15:333-40 pubmed publisher
    Severe preeclampsia is associated with increased neutrophil activation and elevated serum soluble endoglin (sEng) and soluble Flt-1 (sFlt-1) in the maternal circulation...
  9. Fournier B, Parkos C. The role of neutrophils during intestinal inflammation. Mucosal Immunol. 2012;5:354-66 pubmed publisher
    ..In this article, we summarize the beneficial and deleterious roles of neutrophils in the intestine during health and disease and provide an overview of what is known about neutrophil function in the gut. ..

Scientific Experts

More Information


  1. Kulkarni S, Sitaru C, Jakus Z, Anderson K, Damoulakis G, Davidson K, et al. PI3Kβ plays a critical role in neutrophil activation by immune complexes. Sci Signal. 2011;4:ra23 pubmed publisher
    ..These results define PI3Kβ as a potential therapeutic target in inflammatory disease. ..
  2. Murphy A, Woollard K, Suhartoyo A, Stirzaker R, Shaw J, Sviridov D, et al. Neutrophil activation is attenuated by high-density lipoprotein and apolipoprotein A-I in in vitro and in vivo models of inflammation. Arterioscler Thromb Vasc Biol. 2011;31:1333-41 pubmed publisher
    ..reconstituted HDL in patients with peripheral vascular disease was demonstrated to significantly attenuate neutrophil activation. We describe here a novel role for HDL and apoA-I in regulating neutrophil activation using in vitro, in ..
  3. Menegazzi R, Decleva E, Dri P. Killing by neutrophil extracellular traps: fact or folklore?. Blood. 2012;119:1214-6 pubmed publisher
    ..It is concluded that NETs entrap but do not kill microbes...
  4. Dumitru C, Gholaman H, Trellakis S, Bruderek K, Dominas N, Gu X, et al. Tumor-derived macrophage migration inhibitory factor modulates the biology of head and neck cancer cells via neutrophil activation. Int J Cancer. 2011;129:859-69 pubmed publisher
    ..In conclusion, our data indicate that the effects of tumor-derived MIF on neutrophils represent an additional mechanism by which MIF might contribute to tumor progression. ..
  5. Wright H, Chikura B, Bucknall R, Moots R, Edwards S. Changes in expression of membrane TNF, NF-{kappa}B activation and neutrophil apoptosis during active and resolved inflammation. Ann Rheum Dis. 2011;70:537-43 pubmed publisher
    ..These data point to an important role of neutrophils in the abnormal TNF signalling pathways activated in RA and provide new evidence that neutrophils actively contribute to altered cytokine signalling in inflammatory diseases. ..
  6. Mitchell M, King M. Shear-induced resistance to neutrophil activation via the formyl peptide receptor. Biophys J. 2012;102:1804-14 pubmed publisher
    ..The role of shear forces on earlier indicators of neutrophil activation, such as L-selectin shedding and ?(M)?(2) integrin activation, remains unclear...
  7. Li N, Mao D, Lü S, Tong C, Zhang Y, Long M. Distinct binding affinities of Mac-1 and LFA-1 in neutrophil activation. J Immunol. 2013;190:4371-81 pubmed publisher
    ..This work furthers the understandings in the kinetic differences between Mac-1 and LFA-1 and in their biological correlations with molecular activation and structural bases. ..
  8. Carlsen E, Hay C, Henard C, Popov V, Garg N, Soong L. Leishmania amazonensis amastigotes trigger neutrophil activation but resist neutrophil microbicidal mechanisms. Infect Immun. 2013;81:3966-74 pubmed publisher
    ..Parasite uptake resulted in neutrophil activation, oxidative burst, and accelerated neutrophil death...
  9. Rehberg S, Yamamoto Y, Sousse L, Jonkam C, Zhu Y, Traber L, et al. Antithrombin attenuates vascular leakage via inhibiting neutrophil activation in acute lung injury. Crit Care Med. 2013;41:e439-46 pubmed publisher
    To test the hypothesis that restoration of antithrombin plasma concentrations attenuates vascular leakage by inhibiting neutrophil activation through syndecan-4 receptor inhibition in an established ovine model of acute lung injury.
  10. Williams C, Bajt M, Sharpe M, McGill M, Farhood A, Jaeschke H. Neutrophil activation during acetaminophen hepatotoxicity and repair in mice and humans. Toxicol Appl Pharmacol. 2014;275:122-33 pubmed publisher
    ..C57BL/6 mice were subjected to APAP overdose and neutrophil activation status was determined during liver injury and liver regeneration...
  11. Hao J, Meng L, Xu P, Chen M, Zhao M. p38MAPK, ERK and PI3K signaling pathways are involved in C5a-primed neutrophils for ANCA-mediated activation. PLoS ONE. 2012;7:e38317 pubmed publisher
    ..further investigated the signaling pathways of C5a-mediated priming of human neutrophils for ANCA-induced neutrophil activation. The effects of the p38 mitogen-activated protein kinase (p38MAPK) inhibitor (SB202190), extracellular ..
  12. Chen G, Dimitriou I, Milne L, Lang K, Lang P, Fine N, et al. The 3BP2 adapter protein is required for chemoattractant-mediated neutrophil activation. J Immunol. 2012;189:2138-50 pubmed publisher
    ..Our results reveal an obligate requirement for the adapter protein 3BP2 in G protein-coupled receptor-mediated neutrophil function. ..
  13. Ramos Mozo P, Madrigal Matute J, Vega de Céniga M, Blanco Colio L, Meilhac O, Feldman L, et al. Increased plasma levels of NGAL, a marker of neutrophil activation, in patients with abdominal aortic aneurysm. Atherosclerosis. 2012;220:552-6 pubmed publisher
    ..Further studies in larger subjects groups are needed to confirm the association between NGAL and AAA presence and growth. ..
  14. Milara J, Juan G, Peiró T, Serrano A, Cortijo J. Neutrophil activation in severe, early-onset COPD patients versus healthy non-smoker subjects in vitro: effects of antioxidant therapy. Respiration. 2012;83:147-58 pubmed publisher characterized by a rapid decline in the lung function at an early age; however, nothing is known about neutrophil activation in COPD patients...
  15. Kim D, Haynes C. On-chip evaluation of neutrophil activation and neutrophil-endothelial cell interaction during neutrophil chemotaxis. Anal Chem. 2013;85:10787-96 pubmed publisher
    ..This study brings new knowledge about neutrophil chemotaxis in the context of cell-to-cell communications, yielding both fundamental and therapeutically relevant insight. ..
  16. Hueber A, Alves Filho J, Asquith D, Michels C, Millar N, Reilly J, et al. IL-33 induces skin inflammation with mast cell and neutrophil activation. Eur J Immunol. 2011;41:2229-37 pubmed publisher
    ..These results therefore demonstrate that IL-33 may play a role in psoriasis-like plaque inflammation. IL-33 targeting may provide a new treatment strategy for psoriasis. ..
  17. Salomonsson E, Carlsson M, Osla V, Hendus Altenburger R, Kahl Knutson B, Oberg C, et al. Mutational tuning of galectin-3 specificity and biological function. J Biol Chem. 2010;285:35079-91 pubmed publisher
    ..Finally, the mutants have helped to define the differences in fine specificity shown by Xenopus, mouse, and human galectin-3 and, as such, the evidence for adaptive change during evolution...
  18. Xu X, Jackson P, TANNER S, Hardison M, Abdul Roda M, Blalock J, et al. A self-propagating matrix metalloprotease-9 (MMP-9) dependent cycle of chronic neutrophilic inflammation. PLoS ONE. 2011;6:e15781 pubmed publisher
    ..These findings have notable implications to the development unrelenting chronic PMN inflammation in human disease. ..
  19. Thom S, Yang M, Bhopale V, Huang S, Milovanova T. Microparticles initiate decompression-induced neutrophil activation and subsequent vascular injuries. J Appl Physiol (1985). 2011;110:340-51 pubmed publisher
    ..Both MP abatement strategies reduce decompression-induced intravascular neutrophil activation, neutrophil sequestration, and tissue injury documented as elevations of vascular permeability and ..
  20. Lazaar A, Sweeney L, Macdonald A, Alexis N, Chen C, Tal Singer R. SB-656933, a novel CXCR2 selective antagonist, inhibits ex vivo neutrophil activation and ozone-induced airway inflammation in humans. Br J Clin Pharmacol. 2011;72:282-93 pubmed publisher
    ..A CXCR1/2 receptor antagonist has shown activity in an ozone challenge model in humans...
  21. Zarbock A, Ley K. Protein tyrosine kinases in neutrophil activation and recruitment. Arch Biochem Biophys. 2011;510:112-9 pubmed publisher
    ..suggests that different protein tyrosine kinases play key roles in signal transduction pathways regulating neutrophil activation and recruitment to inflammatory sites...
  22. Lindau D, Rönnefarth V, Erbacher A, Rammensee H, Decker P. Nucleosome-induced neutrophil activation occurs independently of TLR9 and endosomal acidification: implications for systemic lupus erythematosus. Eur J Immunol. 2011;41:669-81 pubmed publisher
    ..TLR9 may thus be differently required in the triggering of nucleosome-induced innate immunity and anti-nucleosome B-cell autoimmunity. ..
  23. Remijsen Q, Kuijpers T, Wirawan E, Lippens S, Vandenabeele P, Vanden Berghe T. Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality. Cell Death Differ. 2011;18:581-8 pubmed publisher
    ..This review describes the recent progress made in the identification of the mechanisms involved in NETosis and discusses its interplay with autophagy and apoptosis. ..
  24. Vendrell A, Gravisaco M, Pasetti M, Croci M, Colombo L, Rodriguez C, et al. A novel Salmonella Typhi-based immunotherapy promotes tumor killing via an antitumor Th1-type cellular immune response and neutrophil activation in a mouse model of breast cancer. Vaccine. 2011;29:728-36 pubmed publisher
    ..Typhi vaccine strain as a cancer immunotherapeutic agent. By potentiating the host antitumor immune response, this approach could be a powerful adjunct tool for cancer therapy...
  25. Pillay J, Tak T, Kamp V, Koenderman L. Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences. Cell Mol Life Sci. 2013;70:3813-27 pubmed publisher
    ..In this review, we will attempt to clarify the differences and similarities between neutrophils and G-MDSCs and attempt to facilitate further research. ..
  26. Lecut C, Faccinetto C, Delierneux C, van Oerle R, Spronk H, Evans R, et al. ATP-gated P2X1 ion channels protect against endotoxemia by dampening neutrophil activation. J Thromb Haemost. 2012;10:453-65 pubmed publisher
    ..Previously, we showed that, in addition to their role in platelet activation, ATP-gated P2X(1) ion channels are involved in promoting neutrophil chemotaxis...
  27. MORRISON H, McKee D, Ritter L. Systemic neutrophil activation in a mouse model of ischemic stroke and reperfusion. Biol Res Nurs. 2011;13:154-63 pubmed publisher
    ..neutrophils play a pivotal role in cerebral ischemia reperfusion injury, little is known about systemic neutrophil activation during reperfusion following ischemic stroke in a mouse model...
  28. Yu H, Hsieh P, Chang Y, Chung P, Kuo L, Hwang T. 2-(2-Fluorobenzamido)benzoate ethyl ester (EFB-1) inhibits superoxide production by human neutrophils and attenuates hemorrhagic shock-induced organ dysfunction in rats. Free Radic Biol Med. 2011;50:1737-48 pubmed publisher
    b>Neutrophil activation after trauma-hemorrhagic shock (T/H) has been implicated in the development of multiple organ dysfunction (MOD)...
  29. Mayadas T, Cullere X, Lowell C. The multifaceted functions of neutrophils. Annu Rev Pathol. 2014;9:181-218 pubmed publisher
    ..These newly appreciated contributions of neutrophils are described in the setting of several inflammatory and autoimmune diseases. ..
  30. Malcolm K, Nichols E, Caceres S, Kret J, Martiniano S, Sagel S, et al. Mycobacterium abscessus induces a limited pattern of neutrophil activation that promotes pathogen survival. PLoS ONE. 2013;8:e57402 pubmed publisher
    ..aureus. These studies add to our understanding of M. abscessus virulence and suggest potential targets of therapy...
  31. van der Veen B, Chen M, Muller R, van Timmeren M, Petersen A, Lee P, et al. Effects of p38 mitogen-activated protein kinase inhibition on anti-neutrophil cytoplasmic autoantibody pathogenicity in vitro and in vivo. Ann Rheum Dis. 2011;70:356-65 pubmed publisher
    ..8%; AR-447 6.0 ± 3.4%) at 7 days. This study shows that p38MAPK inhibition markedly reduces ANCA-induced neutrophil activation in vitro...
  32. Thom S, Milovanova T, Bogush M, Yang M, Bhopale V, Pollock N, et al. Bubbles, microparticles, and neutrophil activation: changes with exercise level and breathing gas during open-water SCUBA diving. J Appl Physiol (1985). 2013;114:1396-405 pubmed publisher
    ..enriched air nitrox) would alter annexin V-positive microparticle (MP) production and size changes and neutrophil activation, as well as their relationships to intravascular bubble formation...
  33. Grassi F. Purinergic control of neutrophil activation. J Mol Cell Biol. 2010;2:176-7 pubmed publisher
    ..colleagues show that adenosine 5'-triphosphate release and signaling through purinergic P2 receptors upon neutrophil activation by bacterial and inflammatory stimuli represents an important mechanism for effective neutrophil ..
  34. Zhang S, Rahman M, Zhang S, Wang Y, Herwald H, Jeppsson B, et al. p38 Mitogen-activated protein kinase signaling regulates streptococcal M1 protein-induced neutrophil activation and lung injury. J Leukoc Biol. 2012;91:137-45 pubmed publisher
    ..In conclusion, these findings suggest that targeting the p38 MAPK signaling pathway may open new opportunities to protect against lung injury in streptococcal infections. ..
  35. Delbosc S, Alsac J, Journe C, Louedec L, Castier Y, Bonnaure Mallet M, et al. Porphyromonas gingivalis participates in pathogenesis of human abdominal aortic aneurysm by neutrophil activation. Proof of concept in rats. PLoS ONE. 2011;6:e18679 pubmed publisher
    ..Our results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal ..
  36. Koshio O, Nagao T, Mabuchi A, Ono Y, Suzuki K. Apoptotic signaling in endothelial cells with neutrophil activation. Mol Cell Biochem. 2012;363:269-80 pubmed publisher
    ..These results suggest the possibility that not only TNF-?/CHX and IL-1? but also DS released from PMN and the cell-permeable reactive oxygen species H(2)O(2) induce blood vessel injury through endothelial apoptosis. ..
  37. Jerke U, Rolle S, Dittmar G, Bayat B, Santoso S, Sporbert A, et al. Complement receptor Mac-1 is an adaptor for NB1 (CD177)-mediated PR3-ANCA neutrophil activation. J Biol Chem. 2011;286:7070-81 pubmed publisher intracellular domain, we characterized components of the NB1 signaling complex that are pivotal for neutrophil activation. PR3-ANCA resulted in degranulation and superoxide production in the mNB1(pos)/PR3(high) neutrophils, but ..
  38. Fermino M, Polli C, Toledo K, Liu F, Hsu D, Roque Barreira M, et al. LPS-induced galectin-3 oligomerization results in enhancement of neutrophil activation. PLoS ONE. 2011;6:e26004 pubmed publisher
    ..domain or via its N-terminal part, with LPS from different bacterial strains, enhances the LPS-mediated neutrophil activation in vitro...
  39. Dokken B, La Bonte L, Davis Gorman G, Teachey M, Seaver N, McDonagh P. Glucagon-like peptide-1 (GLP-1), immediately prior to reperfusion, decreases neutrophil activation and reduces myocardial infarct size in rodents. Horm Metab Res. 2011;43:300-5 pubmed publisher
    ..52±0.31 vs. GLP-1 4.78±0.90, TFI, p<0.05). These findings suggest that one mechanism by which GLP-1 decreases reperfusion injury may be the attenuation of PMN-mediated reperfusion injury. ..
  40. Sugama K, Suzuki K, Yoshitani K, Shiraishi K, Kometani T. IL-17, neutrophil activation and muscle damage following endurance exercise. Exerc Immunol Rev. 2012;18:116-27 pubmed
    ..Haematological and biochemical variables such as neutrophil activation marker (myeloperoxidase: MPO), muscle damage marker (myoglobin: Mb) and soluble receptor activator of ..
  41. Laarman A, Mijnheer G, Mootz J, van Rooijen W, Ruyken M, Malone C, et al. Staphylococcus aureus Staphopain A inhibits CXCR2-dependent neutrophil activation and chemotaxis. EMBO J. 2012;31:3607-19 pubmed publisher
    ..produced at the site of infection, plays an important role in antimicrobial host defenses such as neutrophil activation and chemotaxis...
  42. Camous L, Roumenina L, Bigot S, Brachemi S, Fremeaux Bacchi V, Lesavre P, et al. Complement alternative pathway acts as a positive feedback amplification of neutrophil activation. Blood. 2011;117:1340-9 pubmed publisher
    ..Complement-induced neutrophil activation involved mostly C5a and possibly C5b-9 complexes, detected on tumor necrosis factor- and serum-activated ..
  43. van Montfoort M, Stephan F, Lauw M, Hutten B, Van Mierlo G, Solati S, et al. Circulating nucleosomes and neutrophil activation as risk factors for deep vein thrombosis. Arterioscler Thromb Vasc Biol. 2013;33:147-51 pubmed publisher
    ..Our study suggests an association among circulating nucleosomes, activated neutrophils, and presence of DVT in humans, which might have implications for treatment and prevention. ..
  44. Jancinova V, Perecko T, Nosal R, Harmatha J, Smidrkal J, Drabikova K. The natural stilbenoid pinosylvin and activated neutrophils: effects on oxidative burst, protein kinase C, apoptosis and efficiency in adjuvant arthritis. Acta Pharmacol Sin. 2012;33:1285-92 pubmed publisher
    ..Pinosylvin is an effective inhibitor of neutrophil activity, and is potentially useful as a complementary medicine in states associated with persistent inflammation. ..
  45. Abi Abdallah D, Lin C, Ball C, King M, Duhamel G, Denkers E. Toxoplasma gondii triggers release of human and mouse neutrophil extracellular traps. Infect Immun. 2012;80:768-77 pubmed publisher
    ..We propose that NET formation limits infection by direct microbicidal effects on Toxoplasma as well as by interfering with the ability of the parasite to invade target host cells...
  46. Dubois A, Gauthier A, Bréa D, Varaigne F, Diot P, Gauthier F, et al. Influence of DNA on the activities and inhibition of neutrophil serine proteases in cystic fibrosis sputum. Am J Respir Cell Mol Biol. 2012;47:80-6 pubmed publisher
    ..Combining the effects of protease inhibitors with that of DNA-degrading agents could counter the deleterious proteolytic effects of NSPs in CF lung secretions. ..
  47. Costantini C, Micheletti A, Calzetti F, Perbellini O, Pizzolo G, Cassatella M. Neutrophil activation and survival are modulated by interaction with NK cells. Int Immunol. 2010;22:827-38 pubmed publisher
    ..Altogether, our results define a novel interaction within the innate immune system whereby NK cells, by directly modulating neutrophil functions, might contribute to the pathogenesis of inflammatory diseases. ..
  48. Vlahos R, Wark P, Anderson G, Bozinovski S. Glucocorticosteroids differentially regulate MMP-9 and neutrophil elastase in COPD. PLoS ONE. 2012;7:e33277 pubmed publisher
    ..b>Neutrophil activation as assessed by NE release was increased in severe COPD (36-fold, GOLD II vs. IV)...
  49. Amulic B, Cazalet C, Hayes G, Metzler K, Zychlinsky A. Neutrophil function: from mechanisms to disease. Annu Rev Immunol. 2012;30:459-89 pubmed publisher
    ..We focus on emerging issues in the field of neutrophil biology, address questions in this area that remain unanswered, and critically examine the experimental basis for common assumptions found in neutrophil literature. ..
  50. Lange M, Szabo C, Traber D, Horvath E, Hamahata A, Nakano Y, et al. Time profile of oxidative stress and neutrophil activation in ovine acute lung injury and sepsis. Shock. 2012;37:468-72 pubmed publisher
  51. Ambruso D, Ellison M, Thurman G, Leto T. Peroxiredoxin 6 translocates to the plasma membrane during neutrophil activation and is required for optimal NADPH oxidase activity. Biochim Biophys Acta. 2012;1823:306-15 pubmed publisher
    ..Prdx6 supports retention of the active oxidase complex in stimulated plasma membrane, and results with mutant proteins imply that Prdx6 serves an additional biochemical or structural role in supporting optimal NADPH oxidase activity. ..
  52. Dias I, Matthews J, Chapple I, Wright H, Dunston C, Griffiths H. Activation of the neutrophil respiratory burst by plasma from periodontitis patients is mediated by pro-inflammatory cytokines. J Clin Periodontol. 2011;38:1-7 pubmed publisher
    ..This study demonstrates that plasma cytokines may have a role in inducing the hyperactive (IL-8, GM-CSF, IFN-?) and hyper-reactive (IFN-?) neutrophil phenotype seen in periodontitis patients. ..