Effects of bone marrow-derived mononuclear cells on airway and lung parenchyma remodeling in a murine model of chronic allergic inflammation.
We hypothesized that bone marrow-derived mononuclear cells (BMDMC) would attenuate the remodeling process in a chronic allergic inflammation model. C57BL/6 mice were assigned to two groups. In OVA, mice were sensitized and repeatedly challenged with ovalbumin. Control mice (C) received saline under the same protocol. C and OVA were further randomized to receive BMDMC (2 × 10⁶) or saline intravenously 24 h before the first challenge. BMDMC therapy reduced eosinophil infiltration, smooth muscle-specific actin expression, subepithelial fibrosis, and myocyte hypertrophy and hyperplasia, thus causing a decrease in airway hyperresponsiveness and lung mechanical parameters. BMDMC from green fluorescent protein (GFP)-transgenic mice transplanted into GFP-negative mice yielded lower engraftment in OVA. BMDMC increased insulin-like growth factor expression, but reduced interleukin-5, transforming growth factor-β, platelet-derived growth factor, and vascular endothelial growth factor mRNA expression. In conclusion, in the present chronic allergic inflammation model, BMDMC therapy was an effective pre-treatment protocol that potentiated airway epithelial cell repair and prevented inflammatory and remodeling processes.
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Soraia C
SC
Abreu
Mariana A
MA
Antunes
Tatiana
T
Maron-Gutierrez
Fernanda F
FF
Cruz
Luana G R R
LG
Carmo
Debora S
DS
Ornellas
Humberto Carreira
HC
Junior
Alexandre M
AM
Absaber
Edwin R
ER
Parra
Vera L
VL
Capelozzi
Marcelo M
MM
Morales
Patricia R M
PR
Rocco
D056151:Airway Remodeling / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002908:Chronic Disease; D003238:Connective Tissue / Q000502:physiology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D007275:Injections, Intravenous / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000473:pathology / Q000628:therapy*
D036341:Intercellular Signaling Peptides and Proteins; D015848:Interleukin-5; D010047:Ovalbumin