B-1a cells protect mice from sepsis-induced acute lung injury

• Published in: Molecular medicine (Cambridge, Mass.) Mass.), 2018-05, Vol.24 (1), p.26-26, Article 26
• Main Authors: Aziz, Monowar, Ode, Yasumasa, Zhou, Mian, Ochani, Mahendar, Holodick, Nichol E, Rothstein, Thomas L, Wang, Ping
• Format: Article
• Language: English
• Subjects: Abdomen; Acute lung injury; Acute Lung Injury - etiology; Acute Lung Injury - immunology; Acute Lung Injury - pathology; Acute Lung Injury - therapy; Adoptive Transfer; Animals; B-1a cells; B-Lymphocytes - transplantation; Bacterial infections; Chemokines; Cloning; Cytokine storm; Cytokines - immunology; Genotype & phenotype; IL-10; Inflammation; Influenza; Laboratories; Lung - immunology; Lung - pathology; Lungs; Male; Mice, Inbred C57BL; Mice, Mutant Strains; Mortality; Neutrophils; Pathophysiology; Peroxidase - immunology; Sepsis; Sepsis - complications; Sepsis - immunology; Sepsis - pathology; Sepsis - therapy; Streptococcus infections; Tumor necrosis factor-TNF
• ISSN: 1076-1551; 1528-3658
• DOI: 10.1186/s10020-018-0029-2

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. 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-1β) 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. We found that septic mice adoptively transferred with B-1a cells significantly decreased the mRNA and protein levels of IL-6, IL-1β 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-1a 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. Our results demonstrate a novel therapeutic potential of B-1a cells to treat sepsis-induced ALI.