Matrix metalloproteinases (MMPs), a class of enzymes responsible for the degradation of extracellular matrix proteins, play important roles in inflammatory and immune responses. In skin, MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are normally inactive but can be expressed during tissue injury. Both degrade collagen IV and other critical components of the basement membrane zone that separates the epidermis from the dermis. The expression of MMP-2 and -9 was studied in sulfur mustard (SM)-exposed ear skin from mice to determine their role in tissue vesicant injury. Punch biopsies of mouse ears were collected between 6 and 168 h after exposure to 97.5 mM (0.08 mg) SM diluted in CH(2)Cl(2). They were examined histologically and assayed for MMP-2 and -9 expression by gelatinase activity assays, real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. A time-related increase in overall gelatinase activity was observed in SM-treated ears. At 168 h after SM exposure, the relative levels of MMP-9 mRNA were increased 27-fold and MMP-9 protein 9-fold when compared with the control (CH(2)Cl(2) treated) ears. In contrast, there were no observable increases in the MMP-2 mRNA or protein levels between treated and control ears. These observations suggest the differential expression of MMP-2 and -9 during the cutaneous response to SM injury and suggest a role for MMP-9 in SM-induced injury.

Collagen XXIII is a member of the transmembranous subfamily of collagens containing a cytoplasmic domain, a membrane-spanning hydrophobic domain, and three extracellular triple helical collagenous domains interspersed with non-collagenous domains. We cloned mouse, chicken, and human ␣1(XXIII) collagen cDNAs and showed that this non-abundant collagen has a limited tissue distribution in non-tumor tissues. Lung, cornea, brain, skin, tendon, and kidney are the major sites of expression. In contrast, five transformed cell lines were tested for collagen XXIII expression, and all expressed the mRNA. In vivo the ␣1(XXIII) mRNA is found in mature and developing organs, the latter demonstrated using stages of embryonic chick cornea and mouse embryos. Polyclonal antibodies were generated in guinea pig and rabbit and showed that collagen XXIII has a transmembranous form and a shed form. Comparison of collagen XXIII with its closest relatives in the transmembranous subfamily of collagens, types XIII and XXV, which have the same number of triple helical and non-collagenous regions, showed that there is a discontinuity in the alignment of domains but that striking similarities remain despite this.Tissues use specific sets of collagens, often synthesized simultaneously, to achieve and maintain particular functional properties. Most collagens are secreted and assembled within the extracellular environment; however, a growing subclass of collagens are transmembranous and inserted into the plasma membrane in a type II orientation to extend their extracellular collagenous domains from the cell surface.The subclass of transmembranous collagens currently includes types XIII, XVII, XXIII, and XXV, summarized in a recent review (1). The group has also been referred to as the MACITs for membrane-associated collagens with interrupted triple helices (2). Type XIII collagen, the first member of the group identified (3), has an important function in muscle tissue. Engineered genetic mutations in the Col13a1 gene in one case causes cardiovascular defects (4) and in another causes abnormal skeletal muscle myofibers with progressive myopathy that is worsened by exercise (5). Type XIII collagen mediates cell attachment through integrin ␣1␤1 but does not interact through another common collagen receptor, ␣2␤1 (6). The second transmembranous collagen to be identified was type XVII (7), which was known for many years as bullous pemphigoid antigen 2 and BP180 prior to the elucidation of its collagenous nature. Being a component of the hemidesmosome (8), type XVII collagen provides structural integrity to the cornea (9 -11) and skin (12), clearly demonstrated by mutations in the COL17A1 gene that cause epidermolysis bullosa (13, 14). Our laboratories added collagen XXIII to the family of transmembranous collagens by identifying a human EST 3 and using its sequence to clone a fragment of chicken collagen XXIII cDNA to examine its expression in cornea (15). We also cloned the full-length mouse collagen XXIII cDNA sequence and deposited it into GenBan...