Ureaplasma infection-mediated release of matrix metalloproteinase-9 and PGP: a novel mechanism of preterm rupture of membranes and chorioamnionitis

• Published in: Pediatric research Vol. 81; no. 1; pp. 75 - 79
• Main Authors: Lal, Charitharth V., Xu, Xin, Jackson, Patricia, Atkinson, Thomas P., Faye-Petersen, Ona M., Kandasamy, Jegen, Waites, Ken, Biggio, Joseph R., Gaggar, Amit, Ambalavanan, Namasivayam
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2017; Nature Publishing Group
• Subjects: 631/80/86; 692/308/3187; 692/699/255/1318; 692/700/1750; Amniotic Fluid - metabolism; Chorioamnionitis - etiology; Chorioamnionitis - metabolism; Collagen - metabolism; Female; Fetal Membranes, Premature Rupture - etiology; Fetal Membranes, Premature Rupture - metabolism; Humans; Infections; Matrix Metalloproteinase 9 - metabolism; Medicine; Medicine & Public Health; Membranes; Mitochondrial Proteins - metabolism; Models, Biological; Oligopeptides - metabolism; Pediatric Surgery; Pediatrics; Peptide Fragments - metabolism; Pregnancy; Pregnancy Complications, Infectious - metabolism; Premature birth; Proline - analogs & derivatives; Proline - metabolism; Serine Endopeptidases - metabolism; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; translational-investigation; Ureaplasma Infections - complications; Ureaplasma Infections - metabolism
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1038/pr.2016.176

Background: Premature rupture of membranes and preterm delivery are associated with Ureaplasma infection . We hypothesized that Ureaplasma induced extracellular collagen fragmentation results in production of the tripeptide PGP (proline-glycine-proline), a neutrophil chemoattractant. PGP release from collagen requires matrix metalloproteases (MMP-8/MMP-9) along with a serine protease, prolyl endopeptidase (PE). Methods: Ureaplasma culture negative amniotic fluid (indicated preterm birth, n = 8; spontaneous preterm birth, n = 8) and Ureaplasma positive amniotic fluid (spontaneous preterm birth, n = 8) were analyzed by electro-spray ionization-liquid chromatography tandem mass spectrometry for PGP, and for MMP-9 by zymography. PE was evaluated in lysates of U. parvum serovar 3 (Up3) and U. urealyticum serovar 10 (Uu10) by western blotting and activity assay. Results: PGP and MMP-9 were increased in amniotic fluid from spontaneous preterm birth with positive Ureaplasma cultures, but not with indicated preterm birth or spontaneous preterm birth with negative Ureaplasma cultures. Human neutrophils cocultured with Ureaplasma strains showed increased MMP-9 activity. PE presence and activity were noted with both Ureaplasma strains. Conclusion: Ureaplasma spp. carry the protease necessary for PGP release, and PGP and MMP-9 are increased in amniotic fluid during Ureaplasma infection, suggesting Ureaplasma spp. induced collagen fragmentation contributes to preterm rupture of membranes and neutrophil influx causing chorioamnionitis.