4.7 Article

Laminin Triggers Neutrophil Extracellular Traps (NETs) and Modulates NET Release Induced by Leishmania amazonensis

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BIOMEDICINES
卷 10, 期 3, 页码 -

出版社

MDPI
DOI: 10.3390/biomedicines10030521

关键词

laminin; neutrophil extracellular traps (NET); Leishmania amazonensis; extracellular matrix

资金

  1. Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) [247844]
  2. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [424301/2016-4]
  3. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [001]
  4. Mercosur Fund for Structural Convergence (FOCEM) [03/11]

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Neutrophils release neutrophil extracellular traps (NETs) when they interact with different laminin (LM) isoforms. The induction of NETs by laminins is partially inhibited by anti-alpha 6 integrin antibody and requires elastase and peptidylarginine deiminase (PAD)-4. Laminins also enhance the release of NETs triggered by a protozoan parasite and exhibit leishmanicidal activity.
Neutrophils are recruited from the blood and transmigrate through the endothelium to reach tissues, where they are prone to respond through different mechanisms, including the release of neutrophil extracellular traps (NETs). These responses occur in close contact with proteins from the basement membrane and extracellular matrix, where laminins are abundant. Thus, we investigated the interactions between neutrophils and different laminin (LM) isoforms and analyzed the induction of NETs. We showed that neutrophils stimulated with LM isoforms 111, 211, 332, 411, 421, and 511 released NETs. The same occurred when neutrophils interacted with polymerized LMs 111, 411, and 511. LM-induced NETs were partially inhibited by pretreatment of neutrophils with an anti-alpha 6 integrin antibody. Furthermore, NETs triggered by laminins were dependent on elastase and peptidylarginine deiminase (PAD)-4, enzymes that participate in chromatin decondensation. We also found that LMs 411 and LM 511 potentiated the NET release promoted by promastigotes of the protozoan parasite Leishmania, and that NETs stimulated by LMs alone display leishmanicidal activity. The ability of LM to induce NET release may have potential implications for the course of inflammation or infection.

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