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Involvement of matrix metalloproteinases in the cutaneous and ocular response to sulfur mustard

TitleInvolvement of matrix metalloproteinases in the cutaneous and ocular response to sulfur mustard
Publication TypeConference Proceedings
Year of Conference2008
AuthorsGivant-Horwitz V., Amir A., Cohen L., Gutman H., Cohen M., Fishbine E., Turetz J., Brandeis R., Kadar T., Dachir S.
Conference NameProceedings of the U.S. Army Medical Defense Bioscience Review
Volume1, A123
Conference LocationHunt Valley MD

The gelatinases matrix metalloproteinase 2 (MMP-2) and (MMP-9) are involved in extracellular matrix remodeling during physiological and pathological processes. Sulfur mustard (SM) causes acute cutaneous and ocular lesions, followed by delayed pathology. This study aimed to evaluate the involvement of gelatinases in acute and long-term pathology after SM exposure. Hairless guinea pig (HGP) skin and rabbit eyes were exposed to SM vapor. Cutaneous and ocular clinical evaluation was performed daily for the first week and once a week thereafter for 2-4 weeks. Gelatinase activity was measured by zymography at various time points postexposure. Constitutive MMP-2 activity, with no MMP-9 activity, was found in naive HGP skin and in naive rabbit corneas. MMP-9 and MMP-2 activities increased in both skin and cornea after exposure to SM vapor. Whereas MMP-9 activity decreased parallel to spontaneous healing, MMP-2 activity remained elevated. The delayed corneal pathology is characterized mainly by neovascularization. MMP-9 activity and elevated MMP-2 activity were found only in the vascularized tissue of corneas displaying neovascularization. In tear fluid, MMP-9 activity was found throughout the followup period postexposure, in contrast to negligible getatinase activity in the tears of naive rabbits. The pattern of gelatinase activity after SM exposure contributes to the understanding of mechanisms involved in SM injury and may have therapeutic implications, such as the use of MMP inhibitors.

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