Focal Dermal–Epidermal Separation and Fibronectin Cleavage in Basement Membrane by Human Mast Cell Tryptase

Abstract

Mast cell proteases are believed to participate in the basement membrane destruction in blistering diseases. Thus, normal human skin specimens were incubated with purified human skin tryptase or compound 48/80 (a mast cell degranulator) for up to 24 h. Thereafter, the specimens were studied immunohistochemically. Tryptase caused, in the presence and absence of 1,10-phenanthroline, focal dermal-epidermal separation above laminin and almost complete disappearance of the staining of the extra domain A region of cellular fibronectin in and beneath the basement membrane. The immunopositivity of the cell-binding region of fibronectin, laminin, and collagens IV and VII, however, was unaltered. Compound 48/80 induced almost complete dermal-epidermal separation above intact laminin and only focal reduction in the extra domain A region of cellular fibronectin staining. These alterations by compound 48/80 were prevented partially by Nalpha-p-tosyl-L-lysine chloromethyl ketone or 1,10-phenanthroline alone but completely when both inhibitors were present suggesting the involvement of tryptic serine proteinases, probably also tryptase, and metalloproteinases. Preventive effect of N-tosyl-L-phenylalanine chloromethyl ketone was weak suggesting minor function of chymotryptic serine proteinases. When tryptase was incubated with heparin and pure plasma fibronectin, an abrupt decrease in the adherence of cultured keratinocytes on to plastic surface coated with these substances and a gradual plasma fibronectin cleavage to 173, 161, and 28 kDa fragments in sodium dodecyl sulfate-polyacrylamide gel electrophoresis were found. In conclusion, tryptase can cause focal dermal-epidermal separation above laminin in skin specimens but it is not known to what extent the decreased keratinocyte adherence in vitro and fibronectin cleavage are related to this dermal-epidermal separation.

Is there a role for mast cells in psoriasis?

“…Tryptase-positive mast cells are increased in number close to the psoriatic epidermis and, therefore, the enzyme may well aVect the basement membrane and basal keratinocytes. Indeed, tryptase has been found to degrade Wbronectin in the basement membrane zone [87]. In addition, tryptase can activate metalloproteinases, such as MMP-3 and MMP-9 [55, 75,102], and pro-urokinase [174], or it can act as a gelatinase [39].…”

IL-15 induces mast cell migration via a pertussis toxin-sensitive receptor

“…For example histamine increases vascular permeability and rapid expression of P-selectin on the endothelium, leading to increased leakage of plasma and leukocyte rolling, adhesion and extravasation [5,6]. Furthermore, neutral proteases released following activation cleave basement membrane constituents including collagen [7] and fibronectin [8].…”

Mild Exercise Suppresses Exacerbation of Dermatitis in NC/Nga Mice: Correlation with b-endorphin Levels

“…Another study indicated that tryptase could also activate pro MMP-9 [23]. In addition, tryptase has previously been reported to cleave fibronectine in the pericellular matrix of fibroblasts, resulting in separation of the dermal-epidermal junction [20,24]. Although the mast cells are not in direct contact with the basement membrane (BM), the tryptase released as a result of AD could reach this zone, resulting in direct cleavage of the BM components, or indirect cleavage by the activation of MMPs.…”

“…Mast cell granules contain several mediators (TNF-α, PGE 2 and serine proteases) that could directly or indirectly modulate the degradation of the extracellular matrix or activate the proenzyme form of MMPs [19,20]. Previous studies have suggested that mast cell tryptase can activate MMP-1 through the activation of pro MMP-3 [21,22].…”