We recently identified a nuclear variant of the BMP2 growth factor, called nBMP2. In an effort to understand the function of this variant protein, we generated a mouse line in which BMP2 is expressed and functions normally, but nBMP2 is excluded from the nucleus. This novel mutation allows the study of nBMP2 without compromising BMP2 function. To determine whether nBMP2 plays a role in immune function, we performed a series of experiments in which we compared mouse survival, organ weights, immune cells numbers, and bacterial load in wild type and nBmp2NLStm mice following primary and secondary challenges with Staphylococcus aureus. Following primary challenge with S. aureus, wild type and nBmp2NLStm mice showed no differences in survival or bacterial load and generated similar numbers and types of leukocytes, although mutant spleens were smaller than wild type. Secondary bacterial challenge with S. aureus, however, produced differences in survival, with increased mortality seen in nBmp2NLStm mice. This increased mortality corresponded to higher levels of bacteremia in nBmp2NLStm mice and to a reduced enlargement of mutant spleens in response to the secondary infection. Together, these results suggest that the recently described nuclear variant of BMP2 is necessary for efficient secondary immune responses.
Nuclear bone morphogenetic protein 2 (nBMP2) is a nuclear variant of the secreted growth factor BMP‐2. Experiments in nBmp2NLStm mutant mice, which lack nBMP2 in the nucleus, revealed that nBMP2 affects intracellular calcium transport in skeletal muscle and hippocampal neurons. The objective of this study was to determine whether nBMP2 affects the immune system, since activation of lymphocytes and other immune cells depends on intracellular calcium transport. We found that spleens in nBmp2NLStm mutant mice were 28% smaller than in wild type mice. When mutants and wild types were challenged with an intravenous infection of 107 CFU of S. aureus, wild type mouse spleens increased in mass by an average of 63%, while mutant mouse spleens increased by 76% by the third day after infection. Liver and kidney mass were not different between mutant and wild type, either before or after infection. The white pulp of the spleen contains many immune cells, particularly B and T lymphocytes and reduced spleen size in the nBmp2NLStm mutant mice could be caused by a reduced number of lymphocytes migrating to the spleen. Samples of blood, liver, spleen, kidney and lymph nodes cultured three days after infection showed no difference in post infection bacterial load between mutant and wild type, suggesting that the innate immune response is functional in nBmp2NLStm mice.Supported by NIH #AR048839
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