['Previously, we found that percutaneous application of peptidoglycan (PEG) from Staphylococcus aureus increased the number of mast cells in the dermis, as seen in patients with atopic dermatitis. However, the origin of the mast cells infiltrating the dermis was not known. Our aim was to determine the origin of the skin mast cells induced by the percutaneous PEG application in mice.', 'PEG was applied to barrier-disrupted abdominal skin of mice every 5 days. Twenty days after the first application, mast cells were detected in the spleen cells by alcian blue-safranin staining. Expression of mast cell proteases and cytokines in the skin or spleen was investigated by reverse transcription-polymerase chain reaction.', 'Percutaneous application of PEG increased the numbers of alcian blue-positive and safranin-negative mast cells in the spleen. Reverse transcription-polymerase chain reaction analysis of the spleen showed that these mast cells expressed mouse mast cell protease (MMCP)-1, MMCP-4, MMCP-5, and mast cell carboxypeptidase, suggesting that they were immature cells positioned developmentally between mucosal mast cells and connective tissue mast cells. In vitro long-term culture of spleen cells in the presence of PEG induced mast cell development. The features of these mast cells were coincident with those seen in the spleens of PEG-applied mice. Furthermore, when mice were intradermally injected, their skin showed increased levels of expression of mRNAs of MMCP-4, MMCP-5, and mast cell carboxypeptidase, but not MMCP-1. Similar mRNA expression was observed in the skin of PEG-applied mice.'] Does percutaneous application of peptidoglycan from Staphylococcus aureus induce mast cell development in mouse spleen?