title: Hyaluronidase decreases neutrophils infiltration to the inflammatory site.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, 14040-903, Brazil.|Departamento de Farmácia, Universidade Vila Velha, Vila Velha, Espirito Santo, Brazil.
authors.forename: Marcio
authors.initials: M
authors.lastname: Fronza
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg, Germany.
authors.forename: Cornélia
authors.initials: C
authors.lastname: Muhr
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, 14040-903, Brazil.
authors.forename: Denise Sayuri Calheiros
authors.initials: DS
authors.lastname: da Silveira
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, 14040-903, Brazil.
authors.forename: Carlos Artério
authors.initials: CA
authors.lastname: Sorgi
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Stephen Fernandes de Paula
authors.initials: SF
authors.lastname: Rodrigues
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Sandra Helena Poliselli
authors.initials: SH
authors.lastname: Farsky
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, 14040-903, Brazil.
authors.forename: Francisco Wanderley Garcia
authors.initials: FW
authors.lastname: Paula-Silva
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg, Germany.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Merfort
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, 14040-903, Brazil. faccioli@fcfrp.usp.br.
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Faccioli
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001808:Blood Vessels; D002351:Carrageenan; D002448:Cell Adhesion / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D007958:Leukocyte Count; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides; D008297:Male; D008810:Mice, Inbred C57BL
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D002351:Carrageenan; D006821:Hyaluronoglucosaminidase
keywords: Air pouch; Carrageenan; Cytokines; Intravital microscopy; LPS; Leukocyte–endothelial interactions; Lipid mediators; Neutrophil influx