Author | Albuquerque, Cassiano Felippe Gonçalves de | |
Author | Rohwedder, Ina | |
Author | Silva, Adriana Ribeiro | |
Author | Ferreira, Alessandra Silveira | |
Author | Kurz, Angela R. M. | |
Author | Cougoule, Céline | |
Author | Klapproth, Sarah | |
Author | Eggersmann, Tanja | |
Author | Silva, Johnatas D. | |
Author | Oliveira, Gisele Pena DE | |
Author | Capelozzi, Vera Luiza | |
Author | Schlesinger, Gabriel Gutfilen | |
Author | Costa, Edlaine Rijo | |
Author | Marins, Rita de Cassia Elias Estrela | |
Author | Mócsai, Attila | |
Author | Maridonneau-Parini, Isabelle | |
Author | Walzog, Barbara | |
Author | Rocco, Patricia Rieken Macedo | |
Author | Sperandio, Markus | |
Author | Faria Neto, Hugo Caire de Castro | |
Access date | 2018-09-27T16:11:57Z | |
Available date | 2018-09-27T16:11:57Z | |
Document date | 2018 | |
Citation | ALBUQUERQUE, Cassiano Felippe Gonçalves de; et al. The Yin and Yang of Tyrosine Kinase inhibition During experimental Polymicrobial sepsis. Frontiers in Immunology, v.9, Article 901, 16p, Apr. 2018. | pt_BR |
ISSN | 1664-3224 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/29112 | |
Language | eng | pt_BR |
Publisher | Frontiers Media | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Sepse | pt_BR |
Subject in Portuguese | Inflamação | pt_BR |
Subject in Portuguese | tráfico de leucócitos | pt_BR |
Subject in Portuguese | Tirosina Quinases | pt_BR |
Subject in Portuguese | Sepse Polimicrobiana Experimental | pt_BR |
Title | The Yin and Yang of Tyrosine Kinase Inhibition During Experimental Polymicrobial Sepsis | pt_BR |
Type | Article | pt_BR |
DOI | 10.3389/fimmu.2018.00901 | |
Abstract | Neutrophils are the first cells of our immune system to arrive at the site of inflammation. They release cytokines, e.g., chemokines, to attract further immune cells, but also actively start to phagocytose and kill pathogens. In the case of sepsis, this tightly regulated host defense mechanism can become uncontrolled and hyperactive resulting in severe organ damage. Currently, no effective therapy is available to fight sepsis; therefore, novel treatment targets that could prevent excessive inflammatory responses are warranted. Src Family tyrosine Kinases (SFK), a group of tyrosine kinases, have been shown to play a major role in regulating immune cell recruitment and host defense. Leukocytes with SFK depletion display severe spreading and migration defects along with reduced cytokine production. Thus, we investigated the effects of dasatinib, a tyrosine kinase inhibitor, with a strong inhibitory capacity on SFKs during sterile inflammation and polymicrobial sepsis in mice. We found that dasatinib-treated mice displayed diminished leukocyte adhesion and extravasation in tumor necrosis factor-α-stimulated cremaster muscle venules in vivo. In polymicrobial sepsis, sepsis severity, organ damage, and clinical outcome improved in a dose-dependent fashion pointing toward an optimal therapeutic window for dasatinib dosage during polymicrobial sepsis. Dasatinib treatment may, therefore, provide a balanced immune response by preventing an overshooting inflammatory reaction on the one side and bacterial overgrowth on the other side. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil / Ludwig Maximilians University München. Walter Brendel Centre. Department of Cardiovascular Physiology and Pathophysiology. Klinikum der Universität. Munich, Germany / Universidade Federal do Rio de Janeiro. Instituto Biomédico. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Ludwig Maximilians University München. Walter Brendel Centre. Department of Cardiovascular Physiology and Pathophysiology. Klinikum der Universität. Munich, Germany. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil / Ludwig Maximilians University München. Walter Brendel Centre. Department of Cardiovascular Physiology and Pathophysiology. Klinikum der Universität. Munich, Germany. | pt_BR |
Affilliation | Université de Toulouse. Institut de Pharmacologie et de Biologie Structurale. Toulouse, France. | pt_BR |
Affilliation | Ludwig Maximilians University München. Walter Brendel Centre. Department of Cardiovascular Physiology and Pathophysiology. Klinikum der Universität. Munich, Germany. | pt_BR |
Affilliation | Ludwig Maximilians University München. Walter Brendel Centre. Department of Cardiovascular Physiology and Pathophysiology. Klinikum der Universität. Munich, Germany. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo,. Faculdade de Medicina. Laboratório de Genômica Pulmonar. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Farmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Université de Toulouse. Institut de Pharmacologie et de Biologie Structurale. Toulouse, France / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa Clínica em DST e AIDS. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Semmelweis University. Department of Physiology. MTA-SE “Lendület” Inflammation Physiology Research Group. Budapest, Hungry. | pt_BR |
Affilliation | Université de Toulouse. Institut de Pharmacologie et de Biologie Structurale. Toulouse, France. | pt_BR |
Affilliation | Ludwig Maximilians University München. Walter Brendel Centre. Department of Cardiovascular Physiology and Pathophysiology. Klinikum der Universität. Munich, Germany. | pt_BR |
Affilliation | niversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Ludwig Maximilians University München. Walter Brendel Centre. Department of Cardiovascular Physiology and Pathophysiology. Klinikum der Universität. Munich, Germany. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil. | pt_BR |
Subject | sepsos | pt_BR |
Subject | inflammation | pt_BR |
Subject | desatinib | pt_BR |
Subject | Src tyrosine kinase | pt_BR |
Subject | leukocyte trafficking | pt_BR |
Subject | Experimental Polymicrobial Sepsis | pt_BR |