COLLAGENOLYTIC ENZYMES (GELATINASES) AND THEIR INHIBITORS IN HUMAN AMNIOCHORIONIC MEMBRANE

OBJECTIVE: This study was designed to investigate the presence of matr ix metalloproteinase-2 (gelatinase A), matrix metalloproteinase-9 (gel atinase B), and their natural inhibitors in both cultured amniochorion ic membrane and membrane obtained from women with infection-associated preterm labor. STUDY DESIGN: Amniochorionic membranes were collected from women with documented intraamniotic infection and from women not in labor undergoing elective repeat cesarean section with no signs of infection or other complications of pregnancy. Normal membranes were c ultured and exposed to endotoxin and peptidoglycan polysaccharide. Mes senger ribonucleic acid expression for gelatinase A, gelatinase B, and tissue inhibitors of matrix metalloproteinase types 1 and 2 was studi ed with use of reverse transcriptase-polymerase chain reaction and loc alization of messenger ribonucleic acid was accomplished with use of i n situ hybridization. Release of gelatinases from the membranes was st udied with gelatin zymography. Tissue inhibitors of matrix metalloprot einase peptides were localized with use of immunocytochemistry. RESULT S: The expression of matrix metalloproteinase types 2 and 9 was seen i n amniochorionic membranes in culture. Matrix metalloproteinase-2 was seen in membranes from nonlaboring women and in women with intraamniot ic infection, whereas matrix metalloproteinase-g was I;een only in mem branes from women with intraamniotic infection. The matrix metalloprot einase-9 expression could also be induced by lipopolysaccharide or pep tidoglycan polysaccharide stimulation in culture. In situ hybridizatio n localized messenger ribonucleic acid for these matrix metalloprotein ases to both amnion and chorion. Zymogram studies showed the activity of matrix metalloproteinase-2 in normal resting membrane and cultured membrane. Matrix metalloproteinase-9 was induced by culture conditions . Tissue inhibitor of matrix metalloproteinase-l and tissue inhibitor of matrix metalloproteinase-2 messenger ribonucleic acid was seen in n ormal, infected, and cultured membranes. In situ hybridization data in dicated that these messages were mainly produced by chorion, but they were also seen in amnion. Immunohistochemistry demonstrated the presen ce of tissue inhibitor of matrix metalloproteinase-l and tissue inhibi tor of matrix metalloproteinase-e peptides in both amnion and chorion and in cells of the reticular layer of the matrix. CONCLUSION: Normal amniochorionic membrane is a source of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinases. Culture conditions and infection induce matrix metalloproteinase-9 expression and release fr om amniochorion. These findings suggest that these collagenolytic enzy mes may play a role in premature rupture of the membranes in infection , which can lead to preterm labor.