Colocalization of multiple laminin isoforms predominantly beneath hemidesmosomes in the upper lamina densa of the epidermal basement membrane

摘要

Multiple laminin isoforms including laminins 5 (alpha 3 beta 3 gamma 2), 6 (alpha 3 beta 1 gamma 1), 10 (alpha 5 beta 1 gamma 1), and possibly laminins 7 (alpha 3 beta 2 gamma 1) and 11 (alpha 5 beta 2 gamma 1) are present in the epidermal basement membrane. However, only the precise epidermal ultrastructural localization of laminin 5 (alpha 3 beta 3 gamma 2) has been elucidated. We therefore determined the precise expression and ultrastructural localization of the alpha 5, beta 1, beta 2, and gamma 1 chains in the epidermis. The expression of laminin chains in skin samples was analyzed from patients with epidermolysis bullosa (EB, n=15) that harbor defects in specific hemidesmosome (HD)-associated components. The expression of the alpha 5, beta 1, and gamma 1 chains (present in laminins 10/11) and beta 2 chain (laminins 7/11) was unaffected in all intact (unseparated) skin of EB patients including Herlitz junctional EB with laminin-5 defects (n=6). In the basement membrane of human epidermis, the alpha 5, beta 1, beta 2, and gamma 1 chains were expressed but also localized to the dermal vessels. Immunogold electron microscopy of normal human epidermis localized the alpha 5, beta 1, beta 2, and gamma 1 chains to the upper lamina densa, with between 84 and 92 of labeling restricted to beneath the HDs, similar to laminin 5 (n >= 200 gold particles per sample, sample number n=4) but distinct from collagen IV labeling (with only 63 labeling beneath HDs, p<0.001). Taken together, the majority of the alpha 5 beta 1/beta 2 gamma 1 laminin chains are located beneath HDs. This suggests that laminin-10-associated chains have specific functions or molecular interactions beneath HDs in the epidermal basement membrane.