Colocalization of Multiple Laminin Isoforms Predominantly beneath Hemidesmosomes in the Upper Lamina Densa of the Epidermal Basement Membrane

Abstract

S U M M A R Y Multiple laminin isoforms including laminins 5 (a3 b3 g2), 6 (a3 b1 g1), 10 (a5 b1 g1), and possibly laminins 7 (a3 b2 g1) and 11 (a5 b2 g1) are present in the epidermal basement membrane. However, only the precise epidermal ultrastructural localization of laminin 5 (a3 b3 g2) has been elucidated. We therefore determined the precise expression and ultrastructural localization of the a5, b1, b2, and g1 chains in the epidermis. The expression of laminin chains in skin samples was analyzed from patients with epidermolysis bullosa (EB, n515) that harbor defects in specific hemidesmosome (HD)-associated components. The expression of the a5, b1, and g1 chains (present in laminins 10/11) and b2 chain (laminins 7/11) was unaffected in all intact (unseparated) skin of EB patients including Herlitz junctional EB with laminin-5 defects (n56). In the basement membrane of human epidermis, the a5, b1, b2, and g1 chains were expressed but also localized to the dermal vessels. Immunogold electron microscopy of normal human epidermis localized the a5, b1, b2, and g1 chains to the upper lamina densa, with between 84%

Junctional basement membrane anomalies of skin and mucosa in lipoid proteinosis (hyalinosis cutis et mucosae)

“…The lack of lamina densa at the cell process loaded with melanosomes (Fig. 4a) seems to correlate to gaps in BM staining beneath melanocytes observed by others applying IIF and confocal imaging [20].…”

The β3 chain short arm of laminin‐332 (laminin‐5) induces matrix assembly and cell adhesion activity of laminin‐511 (laminin‐10)

“…It is assumed that the b3 short arm of Lm332 activates integrin activity to interact with the integrin-binding sites of Lm332, Lm511, and possibly other laminins, leading to the enhancement of the cell adhesion activity and matrix assembly of these laminins. In this regard, it is noted that Lm332 and Lm511 are colocalized in the epidermal BM [Aumailley and Rousselle, 1999;McMillan et al, 2006]. It was previously reported that the b3 short arm is proteolytically released from Lm332 in human keratinocytes [Nakashima et al, 2005].…”

Blockade of Autoantibody-Initiated Tissue Damage by Using Recombinant Fab Antibody Fragments against Pathogenic Autoantigen

“…24,25 Briefly, cryofixed cryosubstituted samples were embedded in Lowicryl K11M resin and polymerized at Ϫ60°C under UV light. Selected blocks were used to produce ultrathin sections that were incubated with Fabs (80 g/ml), diluted in PBS-based buffer, and washed four times (five minutes each).…”