Inhibitory antibodies against endopeptidase activity of human adamalysin 19

Human adamalysin 19 (hADAM19)/meltrin beta is a member of the ADAM (a disin tegrin and metalloproteinase) family and an active metalloproteinase. It is a new metalloproteinase and disintegrin dendritic cell antigen marker. Ada malysin 19 gene was expressed in normal and transformed tissues and cells s uch as placenta, brain, heart, leukocytes, and colorectal adenocarcinoma SW 480. To develop specific tools to investigate the functions of hADAM19, pep tide antigens were rationally selected and specific polyclonal antibodies ( pAbs) were developed to modulate hADAM19 activity. Amti-metalloproteinase a nd anti-disintegrin domain IgG molecules inhibited the alpha -2-macroglobul in cleavage by bADAM19; however, their pre-immune and anti-pro-domain IgG m olecules did not. Since anti-disintegrin IgG also neutralized the proteolyt ic activity, the disintegrin domain may affect the hADAM19 protein folding and/or substrate binding. These pAbs may be used to specifically localize t he hADAM19 protein in tissues and cells and elucidate its biological and pa thological functions such as processing pro-growth factors. (C) 2001 Academ ic Press.