Microfibril-associated glycoprotein 2 (MAGP2) loss of function has pleiotropic effects in vivo.

Microfibril-associated glycoprotein (MAGP) 1 and 2 are evolutionarily related but structurally divergent proteins that are components of microfibrils of the extracellular matrix. Using mice with a targeted inactivation of Mfap5, the gene for MAGP2 protein, we demonstrate that MAGPs have shared as well as unique functions in vivo. Mfap5(-/-) mice appear grossly normal, are fertile, and have no reduction in life span. Cardiopulmonary development is typical. The animals are normotensive and have vascular compliance comparable with age-matched wild-type mice, which is indicative of normal, functional elastic fibers. Loss of MAGP2 alone does not significantly alter bone mass or architecture, and loss of MAGP2 in tandem with loss of MAGP1 does not exacerbate MAGP1-dependent osteopenia. MAGP2-deficient mice are neutropenic, which contrasts with monocytopenia described in MAGP1-deficient animals. This suggests that MAGP1 and MAGP2 have discrete functions in hematopoiesis. In the cardiovascular system, MAGP1;MAGP2 double knockout mice (Mfap2(-/-);Mfap5(-/-)) show age-dependent aortic dilation. These findings indicate that MAGPs have shared primary functions in maintaining large vessel integrity. In solid phase binding assays, MAGP2 binds active TGFß1, TGFß2, and BMP2. Together, these data demonstrate that loss of MAGP2 expression in vivo has pleiotropic effects potentially related to the ability of MAGP2 to regulate growth factors or participate in cell signaling.

α1-antitrypsin and C-reactive protein levels in tear fluid after continuous contact lens wear.

BACKGROUND: Corneal inflammation has long been associated with contact lens wear and the use of extended-wear lenses enhances the risk of corneal injury. Elucidation of the molecular mediators of contact lens-associated inflammation has the potential to provide injury-identifying markers early in the inflammatory process, as well as determine potential therapeutic targets. METHODS: This cross-over study investigated a potential correlation between overnight contact lens wear and the concentrations of two markers of inflammation, α1-antitrypsin and C-reactive protein, in tear fluid. To obtain baseline measurements, 17 subjects adapted to wearing silicone hydrogel contact lenses wore their prescribed eye glasses for one week, after which tears were collected and ocular health assessed by a licensed optometrist. Subjects then returned to wearing their prescribed silicone hydrogel lenses continuously for one week. A second tear sample was collected and ocular inflammation was again assessed. Enzyme-linked immunosorbent assays were performed on all tear samples for both α1-antitrypsin and C-reactive protein. RESULTS: α1-antitrypsin was significantly (p = 0.01) elevated after continuous contact lens wear, with increases above baseline concentrations averaging 2.48-fold. Optometric assessment of inflammation loosely correlated with levels of this inflammatory marker. C-reactive protein was detected in the tears of subjects at both times and levels were also slightly elevated after extended lens wear, but not significantly (p > 0.5) and not consistently in all subjects. CONCLUSION: The results of this study suggest that α1-antitrypsin in tear fluid may be useful as an early marker of contact lens-associated ocular irritation and inflammation. The presence of C-reactive protein in the tears of contact lens wearers is a novel finding which, while not correlative with either α1-antitrypsin concentrations or clinically observable inflammation, may warrant further study.