Proinflammatory properties of the human S100 protein S100A12

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 (similar to 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 mollocytes by tumor necrosis factor alpha (6 h); induction by lipopolysaccharide (LPS) was sustained (12-48 h), A12 may contribute to leukocyte migration in chronic inflammatory responses.