Matrix metalloproteinases as mediators of tissue injury in different forms of cutaneous lupus erythematosus.

BACKGROUND: Matrix metalloproteinases (MMPs) contribute to tissue destruction, regeneration, inflammation and apoptosis and several of them are upregulated by ultraviolet (UV) radiation in skin. Although some MMPs associate with organ manifestations of systemic lupus erythematosus (SLE), their role in cutaneous lupus erythematosus (LE) is elusive. OBJECTIVES: Our aim was to evaluate the expression of MMPs in SLE, subacute cutaneous LE (SCLE) and discoid LE (DLE) skin lesions and their relation to apoptosis and epidermal changes. METHODS: Lesional skin biopsies from 20 patients with SLE, 20 with DLE and 17 with SCLE, and from UVA/UVB-photoprovoked skin of healthy volunteers were immunostained using antibodies to multiple MMPs and tissue inhibitors of metalloproteinases (TIMPs). The TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling) method was used for detection of apoptosis. RESULTS: MMP-3, -10, -19 and -26 were abundantly expressed by keratinocytes in SLE, DLE and SCLE skin samples. MMP-7 was detected in keratinocytes in regions of oedema and vacuolization especially in SLE and SCLE, while MMP-14 was only occasionally observed in keratinocytes. Photoprovocation did not induce MMP-10 or -26 expression in skin of healthy volunteers. Epithelial TIMP-1 expression was low while occasional positive fibroblasts were seen in the dermis. TIMP-3 was abundantly expressed in the epidermis, endothelial cells and macrophages. CONCLUSIONS: Different subtypes of cutaneous LE are fairly similar in their MMP expression profile. MMP-3 and -10 mediate both epidermal changes and dermal tissue remodelling but are not present in lymphocytes. Low expression of TIMP-1 suggests that lupus skin is characterized by proteolytic events, and targeted action using selective MMP inhibitors may reduce lupus-induced damage in inflamed tissues.

The anatomy of the human promontory for laser Doppler flowmetry.

Studies of the dynamic characteristics of cochlear blood flow (CBF) utilizing laser Doppler flowmetry (LDF) in laboratory animals have provided a new approach to the understanding of control mechanisms of CBF and the role of the CBF in cochlear disorders. However, few studies exist indicating that LDF of human CBF may be possible. Since bone thickness, density, structure characteristics, and blood flow all greatly affect LDF recording, we examined the anatomy of the human promontory for inter-individual variations in thickness, quality and vascularity of the bone and mucosa and recorded middle ear topographic relationships to the underlying cochlear lateral wall vasculature. Temporal bones from 21 cadavers without known premortem histories of ear disease were obtained. India ink was infused selectively via the vertebral or carotid system to study the origin of bone/ mucosa circulation to the otic capsule. Light microscopy revealed that the human promontory was characterized as cortical bone having few blood vessels. The thickness of the bone measured at four horizontal levels and mucosa at the top of promontory and anteriorly around the tympanic plexus varied from 1.67 +/- 0.64 to 1.13 +/- 0.26 mm for bone and 0.06-0.13 mm for mucosa. The thinnest bone was found around the tympanic plexus, where the bone thickness varied from 0.6 to 1.2 mm. Previous data indicate that current LDF instruments can provide a linear measure of blood flow through bone thicknesses of 1-3 mm or more (depending on the type of bone). Data from the current study indicate that direct valid dynamic measures of CBF are possible in humans. Since the optimal area available is small, the topography of the middle ear should be well known and the recording site well defined to obtain valid results.