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 [Ca(2+)]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 (approximately 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 alpha (6 h); induction by lipopolysaccharide (LPS) was sustained (12-48 h). A12 may contribute to leukocyte migration in chronic inflammatory responses.
Yang
Z
Z
Cytokine Research Unit, School of Pathology, The University of New South Wales, Kensington 2052, Australia.
Tao
T
T
Raftery
M J
MJ
Youssef
P
P
Di Girolamo
N
N
Geczy
C L
CL
D000199:Actins / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D001704:Biopolymers / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D040501:Calgranulin A; D040502:Calgranulin B; D002478:Cells, Cultured / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects*; D008264:Macrophages / Q000737:chemistry / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009504:Neutrophils / Q000737:chemistry / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000378:metabolism; D000067616:S100A12 Protein; D013047:Specific Pathogen-Free Organisms; D013582:Synovial Fluid / Q000737:chemistry; D013583:Synovial Membrane / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000199:Actins; D000943:Antigens, Differentiation; D001704:Biopolymers; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D008070:Lipopolysaccharides; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D014409:Tumor Necrosis Factor-alpha