Journal Article

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

Ode, Yasumasa, Zhou, Mian, Rothstein, Thomas L., Aziz, Monowar, Ochani, Mahendar, Wang, Ping, Holodick, Nichol E.

2018

Overview

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-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. Results 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. Conclusions Our results demonstrate a novel therapeutic potential of B-1a cells to treat sepsis-induced ALI.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: 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 / Biomedical and Life Sciences / Biomedicine / 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 / Molecular Medicine / Mortality / Neutrophils / Pathophysiology / Peroxidase - immunology / Research Article / Sepsis / Sepsis - complications / Sepsis - immunology / Sepsis - pathology / Sepsis - therapy / Streptococcus infections / Tumor necrosis factor-TNF