title: Insult-dependent effect of bone marrow cell therapy on inflammatory response in a murine model of extrapulmonary acute respiratory distress syndrome.
abstract: BACKGROUND
  Administration of bone marrow-derived cells produces beneficial effects in experimental extrapulmonary acute respiratory distress syndrome (ARDS). However, there are controversies regarding the effects of timing of cell administration and initial insult severity on inflammatory response. We evaluated the effects of bone marrow-derived mononuclear cells (BMDMC) in two models of extrapulmonary ARDS once lung morphofunctional changes had already been installed.
  
  
  METHODS
  BALB/c mice received lipopolysaccharide (LPS) intraperitoneally (5 mg/kg in 0.5 ml saline) or underwent cecal ligation and puncture (CLP). Control mice received saline intraperitoneally (0.5 ml) or underwent sham surgery. At 24 hours, groups were further randomized to receive saline or BMDMC (2 × 10(6)) intravenously. Lung mechanics, histology, and humoral and cellular parameters of lung inflammation and remodeling were analyzed 1, 3 and 7 days after ARDS induction.
  
  
  RESULTS
  BMDMC therapy led to improved survival in the CLP group, reduced lung elastance, alveolar collapse, tissue and bronchoalveolar lavage fluid cellularity, collagen fiber content, and interleukin-1β and increased chemokine (keratinocyte-derived chemokine and monocyte chemotactic protein-1) expression in lung tissue regardless of the experimental ARDS model. Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in lung tissue increased after cell therapy depending on the insult (LPS or CLP).
  
  
  CONCLUSIONS
  BMDMC therapy at day 1 successfully reduced lung inflammation and remodeling, thus contributing to improvement of lung mechanics in both extrapulmonary ARDS models. Nevertheless, the different inflammatory responses induced by LPS and CLP resulted in distinct effects of BMDMC therapy. These data may be useful in the clinical setting, as they suggest that the type of initial insult plays a key role in the outcome of treatment.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Maron-Gutierrez
authors.forename: Johnatas Dutra
authors.initials: JD
authors.lastname: Silva
authors.forename: Fernanda Ferreira
authors.initials: FF
authors.lastname: Cruz
authors.forename: Samantha
authors.initials: S
authors.lastname: Alegria
authors.forename: Debora Gonçalves
authors.initials: DG
authors.lastname: Xisto
authors.forename: Edson Fernandes
authors.initials: EF
authors.lastname: Assis
authors.forename: Hugo Caire
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.forename: Claudia Chimisso
authors.initials: CC
authors.lastname: Dos Santos
authors.forename: Marcelo Marcos
authors.initials: MM
authors.lastname: Morales
authors.forename: Patricia Rieken Macedo
authors.initials: PR
authors.lastname: Rocco
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D064987:Cell- and Tissue-Based Therapy; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000637:transplantation; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000276:immunology / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D018925:Chemokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C074302:keratinocyte-derived chemokines