Differential expression of S100A10 protein in leukocytes and its effects on monocyte emigration from bone marrow.

Abstract

Although the importance of the unique member of S100 EF-hand family, S100A10 in health and disease is well appreciated, a precise characterization of S100A10 expression still remains elusive. To this purpose, we generated a knock-in mouse line in which downstream of the coding sequence of the S100a10 gene was inserted IRES-mCherry-pA sequence. Interestingly, mCherry fluorescence was widely distributed in splenic myeloid and lymphoid cells, whereas neutrophils showed a negligible mCherry level. By taking advantage of these reporter mice, we found Ly6C+ monocytes expressed the highest levels of S100A10 and bound significantly more plasminogen compared with the other respective leukocyte subsets. Furthermore, we demonstrated that S100A10 was required for emigration of Ly6C+ monocytes from bone marrow by mainly affecting CCR2 cell surface presentation. S100a10-/- mice had fewer circulating Ly6C+ monocytes and, after challenged with thioglycolate, accumulated less CCR2+ monocytes in bone marrow. However, S100A10 was not necessary for efficient neutrophil recruitment from the blood to inflamed tissue. These findings provide evidence that S100A10 is critical for monocyte mobilization and suggest its differential regulatory roles for monocyte and neutrophil chemoattractants in leukocyte homeostasis. Thus, targeting the S100A10-CCR2 pathway may be an attractive approach to regulate inflammatory responses and infectious diseases.