Journal article
Therapeutic role for mannose-binding lectin in cigarette smoke-induced lung inflammation? Evidence from a murine model
American Journal of Respiratory Cell and Molecular Biology, Vol.42(2), pp.235-242
2010
PMID: 19411612
Abstract
Defective efferocytosis in the airway may perpetuate inflammation in smokers with/without chronic obstructive pulmonary disease. Mannose-binding lectin (MBL) improves efferocytosis in vitro; however, the effects of in vivo administration are unknown. MBL circulates in complex with MBL-associated serine proteases (MASPs), and efferocytosis involves activation of cytoskeletalremodeling molecules, including Rac1/2/3. We hypothesized that MBL would improve efferocytosis in vivo, and that possible mechanisms for this effect would include up-regulation of Rac1/2/3 or MASPs.Weused a smokingmousemodel to investigate the effects of MBLon efferocytosis.MBL(20μg/ 20 g mouse) was administered via nebulizer to smoke-exposed mice. In lung tissue (disaggregated) and bronchoalveolar lavage (BAL), we investigated leukocyte counts, apoptosis, andthe ability of alveolarandtissuemacrophages to phagocytose apoptotic murine epithelial cells. In human studies, flow cytometry, ELISA, and RT-PCR were used to investigate the effects of MBL on efferocytosis, Rac1/2/3, and MASPs. Smokeexposed mice showed significantly reduced efferocytosis in BAL and tissue. Efferocytosis was significantly improved by MBL (BAL: control, 26.2%; smoke-exposed, 17.66%; MBL 1 smoke-exposed, 27.8%; tissue: control, 35.9%; smoke-exposed, 21.6%; MBL 1 smoke-exposed, 34.5%). Leukocyte/macrophage counts were normalized in smoke-exposed mice treated with MBL. Inhumanstudies, MBL was reduced in chronic obstructive pulmonary disease and in smokers, and was significantly correlated with reduced efferocytosis ex vivo. MASPs were not detected in BAL, and were not produced by alveolar or tissue macrophages. MBL significantly increased macrophage expression of Rac1/2/3. We provide evidence for Rac1/2/3 involvement in the MBL-mediated improvement in efferocytosis, and a rationale for investigating MBL as a supplement to existing therapies in smoking-related lung inflammation.
Details
- Title
- Therapeutic role for mannose-binding lectin in cigarette smoke-induced lung inflammation? Evidence from a murine model
- Authors
- Sandra Hodge (Author) - Royal Adelaide HospitalGeoffrey M Matthews (Author) - Royal Adelaide HospitalMelinda M Dean (Author) - Australian Red Cross Blood ServiceJessica Ahern (Author) - Royal Adelaide HospitalMichael Djukic (Author) - Royal Adelaide HospitalGreg L Hodge (Author) - The University of AdelaideHubertus Jersmann (Author) - The University of AdelaideMark D Holmes (Author) - Royal Adelaide HospitalPaul N Reynolds (Author) - Royal Adelaide Hospital
- Publication details
- American Journal of Respiratory Cell and Molecular Biology, Vol.42(2), pp.235-242
- Publisher
- American Thoracic Society
- Date published
- 2010
- DOI
- 10.1165/rcmb.2008-0486OC
- ISSN
- 1044-1549; 1535-4989; 1044-1549
- PMID
- 19411612
- Organisation Unit
- School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99513884502621
- Output Type
- Journal article
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- Domestic collaboration
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Respiratory System
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