Differential secretion of matrix metalloproteinase-2 and -9 after selective infection with group B streptococci in human fetal membranes.
OBJECTIVE
This study evaluated the secretions of zymogen and active forms of matrix metalloproteinase (MMP)-9 and MMP-2 and their specific inhibitors, TIMP-1 and TIMP-2 by fetal membranes stimulated with group B Streptoccocci (GBS).


METHODS
We used an in vitro experimental model that allowed us to estimate the individual contribution of the amnion (AM) and the choriodecidua (CHD) to the microbial insult. Membranes were obtained after delivery by elective cesarean delivery from women at 37 to 40 weeks of gestation without evidence of either active labor or intrauterine infection. Membranes were mounted in Transwell devices (Costar, New York, NY), physically separating the upper and lower chambers; 1 x 10(6) CFU of GBS was added to either AM or CHD and the secretions and gelatinolytic activity of MMP-2 and MMP-9 were measured in both compartments by enzyme-linked immunosorbent assay (ELISA) and zymography. TIMPs secretion was measured by ELISA. Both MMPs were immunolocalized in tissue sections.


RESULTS
The simultaneous stimulation at both sides was followed by increases of proMMP-9 (85.0 +/- 18.63 pg/mL) and proMMP-2 (4.10 +/- 1.90 ng/mL) in the CHD (P <.05). When only one side of the membrane was stimulated, the secretion level of proMMP-2 increased 2.3-fold and that of proMMP-9 2.5-fold in the CHD. The active forms of both enzymes did not change with any modality of stimulation. The secretion level of both TIMPs remained without significant changes. CHD and AM were positive for immunoreactive MMP-2 and MMP-9.


CONCLUSIONS
We propose that infection of fetal membranes with GBS is followed by active secretion of MMP and the CHD is the principal source of these mediators of extracellular matrix degradation.
Zaga-Clavellina
Verónica
V
Direction of Research, Nacional de Perinatologia, Mexico City, Mexico. zaga@universo.com
Merchant-Larios
Horacio
H
García-López
Guadalupe
G
Maida-Claros
Rolando
R
Vadillo-Ortega
Felipe
F
D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000378:metabolism* / Q000382:microbiology*; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000382:microbiology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000503:physiopathology*; D011263:Pregnancy Trimester, Third; D013290:Streptococcal Infections / Q000503:physiopathology*; D013292:Streptococcus agalactiae; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9