Proinflammatory properties of the human S100 protein S100A12

Publisher Website
Google Scholar
Abstract
S100 proteins represent a new class of chemoattractants. Here we extend earlier evidence for the proinflammatory properties of human S100A12. A12 induced migration of monocytoid cells, with optimal activity at 10−10 M and potency of >10−9 M C5a. Neutrophils were poorly responsive, and lymphocyte migration was not affected. Actin polymerization in monocytoid cells was accompanied by a sustained [Ca2+]i flux of a magnitude comparable with C5a. A12 elicited a transient infiltration of neutrophils (4–8 h) and more delayed recruitment of monocytes (8–24 h) in vivo. A12 (∼70 nM) was present in synovial fluid (SF) from rheumatoid arthritis patients, and synovium contained A12-positive neutrophils in the sublining and interstitial region, often surrounding the perivasculature but rarely in the synovial lining layer, although some macrophages were positive. The A12 gene was transiently up-regulated in monocytes by tumor necrosis factor α (6 h); induction by lipopolysaccharide (LPS) was sustained (12–48 h). A12 may contribute to leukocyte migration in chronic inflammatory responses.