PMID- 24406030 OWN - NLM STAT- MEDLINE DCOM- 20140911 LR - 20211021 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 4 IP - 5 DP - 2013 Oct 13 TI - Insult-dependent effect of bone marrow cell therapy on inflammatory response in a murine model of extrapulmonary acute respiratory distress syndrome. PG - 123 LID - 10.1186/scrt334 [doi] AB - INTRODUCTION: 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 x 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-1beta 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. FAU - Maron-Gutierrez, Tatiana AU - Maron-Gutierrez T FAU - Silva, Johnatas Dutra AU - Silva JD FAU - Cruz, Fernanda Ferreira AU - Cruz FF FAU - Alegria, Samantha AU - Alegria S FAU - Xisto, Debora Goncalves AU - Xisto DG FAU - Assis, Edson Fernandes AU - Assis EF FAU - Castro-Faria-Neto, Hugo Caire AU - Castro-Faria-Neto HC FAU - Dos Santos, Claudia Chimisso AU - Dos Santos CC FAU - Morales, Marcelo Marcos AU - Morales MM FAU - Rocco, Patricia Rieken Macedo AU - Rocco PR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131013 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (Chemokine CCL2) RN - 0 (Chemokines) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-1beta) RN - 0 (RNA, Messenger) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 147037-79-4 (keratinocyte-derived chemokines) SB - IM CIN - Stem Cell Res Ther. 2013;4(6):143. PMID: 24279925 MH - Animals MH - Bone Marrow Cells/*cytology MH - *Cell- and Tissue-Based Therapy MH - Chemokine CCL2/genetics/metabolism MH - Chemokines/genetics/metabolism MH - Disease Models, Animal MH - Female MH - Inflammation Mediators/*metabolism MH - Intercellular Adhesion Molecule-1/genetics/metabolism MH - Interleukin-1beta/genetics/metabolism MH - Leukocytes, Mononuclear/cytology/transplantation MH - Lung/metabolism/pathology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - RNA, Messenger/metabolism MH - Respiratory Distress Syndrome/immunology/pathology/therapy MH - Time Factors MH - Vascular Cell Adhesion Molecule-1/genetics/metabolism PMC - PMC3856598 EDAT- 2014/01/11 06:00 MHDA- 2014/09/12 06:00 PMCR- 2013/10/13 CRDT- 2014/01/11 06:00 PHST- 2013/05/14 00:00 [received] PHST- 2013/10/03 00:00 [accepted] PHST- 2014/01/11 06:00 [entrez] PHST- 2014/01/11 06:00 [pubmed] PHST- 2014/09/12 06:00 [medline] PHST- 2013/10/13 00:00 [pmc-release] AID - scrt334 [pii] AID - 10.1186/scrt334 [doi] PST - epublish SO - Stem Cell Res Ther. 2013 Oct 13;4(5):123. doi: 10.1186/scrt334.