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Hyaluronidase decreases neutrophils infiltration to the inflammatory site

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Abstract

Objective

To evaluate the in vivo anti-inflammatory potential of bovine hyaluronidase (HYAL) using two different models of acute inflammation.

Methods

Air pouches were produced in the dorsal subcutaneous of mice and injected with phosphate saline solution or HYAL. The antiinflammatory action of HYAL was evaluated in carrageenan (Cg)-inflamed air pouches. After 4 and 24 h the cellular influx, protein exudation, cytokines and lipid mediators were evaluated. The action of HYAL on the rolling and adhesion of leukocytes was investigated in the LPS-stimulated mesenteric microcirculation by intravital microscopic.

Results

Treatment with HYAL reduced the cellular influx and protein exudation in non-inflamed and inflamed air pouches. HYAL treatment of Cg-inflamed air pouch reduced the production of tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), leukotriene B4 (LTB4) and LTC4, whereas prostaglandins E2 (PGE2) and D2 (PGD2) concentrations were unchanged. Histological analyses showed that HYAL administration diminished cell infiltration in the air-pouch lining. In LPS-stimulated mesenteric microcirculation, HYAL usage decreased rolling and adhesion of leukocytes, but did not affect the blood vessels diameters.

Conclusion

The results demonstrate that HYAL inhibited cellular recruitment, edema formation and pro-inflammatory mediators production, resulting in decreased adherence of leukocytes to blood vessels and tissue infiltration. Our data suggest that HYAL may be considered an effective candidate to ameliorate acute inflammation.

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Acknowledgments

The authors are grateful to the São Paulo Research Foundation (FAPESP, Grants# 2011/23992-3; 2009/07169-5), to the German Academic Exchange Service (DAAD) and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support. S.F. Rodrigues is a postdoctoral fellow from FAPESP (2011/02438-8).

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    Authors and Affiliations

    1. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, 14040-903, Brazil

      Marcio Fronza, Denise Sayuri Calheiros da Silveira, Carlos Artério Sorgi, Francisco Wanderley Garcia Paula-Silva & Lúcia Helena Faccioli

    2. Departamento de Farmácia, Universidade Vila Velha, Vila Velha, Espirito Santo, Brazil

      Marcio Fronza

    3. Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg, Germany

      Cornélia Muhr & Irmgard Merfort

    4. Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

      Stephen Fernandes de Paula Rodrigues & Sandra Helena Poliselli Farsky

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    1. Marcio Fronza
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    Correspondence to Lúcia Helena Faccioli.

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    Responsible Editor: Mauro Teixeira.

    M. Fronza and C. Muhr equally contributed to this work.

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    Fronza, M., Muhr, C., da Silveira, D.S.C. et al. Hyaluronidase decreases neutrophils infiltration to the inflammatory site. Inflamm. Res. 65, 533–542 (2016). https://doi.org/10.1007/s00011-016-0935-0

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