Inhibitory antibodies against endopeptidase activity of human adamalysin 19

Human adamalysin 19 (hADAM19)/meltrin beta is a member of the ADAM (a disintegrin and metalloproteinase) family and an active metalloproteinase. It is a new metalloproteinase and disintegrin dendritic cell antigen marker. Adamalysin 19 gene was expressed in normal and transformed tissues and cells such as placenta, brain, heart, leukocytes, and colorectal adenocarcinoma SW480. To develop specific tools to investigate the functions of hADAM19, peptide antigens were rationally selected and specific polyclonal antibodies (pAbs) were developed to modulate hADAM19 activity. Amti-metalloproteinase and anti-disintegrin domain IgG molecules inhibited the alpha -2-macroglobulin cleavage by bADAM19; however, their pre-immune and anti-pro-domain IgG molecules did not. Since anti-disintegrin IgG also neutralized the proteolytic activity, the disintegrin domain may affect the hADAM19 protein folding and/or substrate binding. These pAbs may be used to specifically localize the hADAM19 protein in tissues and cells and elucidate its biological and pathological functions such as processing pro-growth factors. (C) 2001 Academic Press.