Journal
MOLECULAR MEDICINE
Volume 24, Issue -, Pages -Publisher
SPRINGER
DOI: 10.1186/s10020-018-0029-2
Keywords
B-1a cells; Sepsis; Acute lung injury; Inflammation; Neutrophils; IL-10
Funding
- National Institutes of Health (NIH) [R35GM118337, R01GM053008, R01GM057468, R01AI029690]
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Background: Sepsis morbidity and mortality are aggravated by acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Mouse B-1a cells are a phenotypically and functionally unique sub-population of B cells, providing immediate protection against infection by releasing natural antibodies and immunomodulatory molecules. We hypothesize that B-1a cells ameliorate sepsis-induced ALI. Methods: Sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP). PBS or B-1a cells were adoptively transferred into the septic mice intraperitoneally. After 20 h of CLP, lungs were harvested and assessed by PCR and ELISA for pro-inflammatory cytokines (IL-6, IL-1 beta) and chemokine (MIP-2) expression, by histology for injury, by TUNEL and cleaved caspase-3 for apoptosis, and by myeloperoxidase (MPO) assay for neutrophil infiltration. Results: We found that septic mice adoptively transferred with B-1a cells significantly decreased the mRNA and protein levels of IL-6, IL-1 beta and MIP-2 in the lungs compared to PBS-treated mice. Mice treated with B-1a cells showed dramatic improvement in lung injury compared to PBS-treated mice after sepsis. We found apoptosis in the lungs was significantly inhibited in B-1a cell injected mice compared to PBS-treated mice after sepsis. B-1a cell treatment significantly down-regulated MPO levels in the lungs compared to PBS-treated mice in sepsis. The protective outcomes of B-la cells in ALI was further confirmed by using B-1a cell deficient CD19(-/-) mice, which showed significant increase in the lung injury scores following sepsis as compared to WT mice. Conclusions: Our results demonstrate a novel therapeutic potential of B-1a cells to treat sepsis-induced ALI.
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