Mobilization and margination of bone marrow Gr-1high monocytes during subclinical endotoxemia predisposes the lungs toward acute injury
| Autor: | Kenji Wakabayashi, Louise Tatton, Justina O. Dokpesi, Nico van Rooijen, Masao Takata, Kieran P. O'Dea, Michael R. Wilson |
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| Přispěvatelé: | Molecular cell biology and Immunology, CCA - Immuno-pathogenesis |
| Rok vydání: | 2009 |
| Předmět: |
Lipopolysaccharides
Male Immunology Acute Lung Injury Dose-Response Relationship Immunologic Vascular permeability Bone Marrow Cells Lung injury Systemic inflammation Monocytes Article Sepsis Capillary Permeability chemistry.chemical_compound Mice Cell Movement Immunology and Allergy Medicine Animals business.industry Monocyte Macrophages Zymosan Cell Differentiation medicine.disease Endotoxemia Mice Inbred C57BL medicine.anatomical_structure chemistry Tumor necrosis factor alpha Receptors Chemokine Bone marrow Endothelium Vascular medicine.symptom Inflammation Mediators business |
| Zdroj: | O'Dea, K P, Wilson, M, Dokpesi, J O, Wakabayashi, K, Tatton, L, van Rooijen, N & Takata, M 2009, ' Mobilization and Margination of Bone Marrow Gr-1(high) Monocytes during Subclinical Endotoxemia Predisposes the Lungs toward Acute Injury ', Journal of Immunology, vol. 182, no. 2, pp. 1155-1166 . https://doi.org/10.4049/jimmunol.182.2.1155 Journal of Immunology, 182(2), 1155-1166. American Association of Immunologists |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.182.2.1155 |
| Popis: | The specialized role of mouse Gr-1high monocytes in local inflammatory reactions has been well documented, but the trafficking and responsiveness of this subset during systemic inflammation and their contribution to sepsis-related organ injury has not been investigated. Using flow cytometry, we studied monocyte subset margination to the pulmonary microcirculation during subclinical endotoxemia in mice and investigated whether marginated monocytes contribute to lung injury in response to further septic stimuli. Subclinical low-dose i.v. LPS induced a rapid (within 2 h), large-scale mobilization of bone marrow Gr-1high monocytes and their prolonged margination to the lungs. With secondary LPS challenge, membrane TNF expression on these premarginated monocytes substantially increased, indicating their functional priming in vivo. Zymosan challenge produced small increases in pulmonary vascular permeability, which were markedly enhanced by the preadministration of low-dose LPS. The LPS-zymosan-induced permeability increases were effectively abrogated by pretreatment (30 min before zymosan challenge) with the platelet-activating factor antagonist WEB 2086 in combination with the phosphatidylcholine-phospholipase C inhibitor D609, suggesting the involvement of platelet-activating factor/ceramide-mediated pathways in this model. Depletion of monocytes (at 18 h after clodronate-liposome treatment) significantly attenuated the LPS-zymosan-induced permeability increase. However, restoration of normal LPS-induced Gr-1high monocyte margination to the lungs (at 48 h after clodronate-liposome treatment) resulted in the loss of this protective effect. These results demonstrate that mobilization and margination of Gr-1high monocytes during subclinical endotoxemia primes the lungs toward further septic stimuli and suggest a central role for this monocyte subset in the development of sepsis-related acute lung injury. |
| Databáze: | OpenAIRE |
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