Early events after skin injury: Observations on changes in Langerhans cells and Birbeck granules with role of phosphorylase kinase in the injury pathway

Madalene CY Heng; Ming K Heng

Madalene CY Heng Department of Medicine, David Geffen School of Medicine, UCLA, California, USA
Ming K Heng Department of Medicine, David Geffen School of Medicine, UCLA, California, USA

Keywords: Birbeck granules, Injury pathway, Langerhans cells, Phosphorylase kinase, Psoriasis

Abstract

Background and Aim: To evaluate the role of Langerhans cells (LCs) in the early events of the injury pathway, we studied activated and unactivated LCs in sequential biopsies from uninvolved skin of psoriatic and nonpsoriatic individuals using immunocytochemistry and electron microscopy. Methods: Tape-stripping injury was used for cell activation. Changes suggestive of LC activation were observed as early as 5–30 min following tape-stripping. These consisted of abundant Golgi cisternae, proliferation of rough endoplasmic reticulum consistent with increased protein synthesis, increased folds and waviness of the nuclear membranes, and development of migratory status as shown by shortening of dendritic processes and presence of spaces around the LCs from detachment of the cell-membranes from the adjacent keratinocytes. Results: There were notable changes in Birbeck granules (BGs) in LCs, with an inverse correlation of BG density with cell activation as early as 5 min after tape-stripping. The BG was most abundant in the unactivated LCs, and least numerous after activation. With cell activation, BG was observed to be few and unstacked, with isolated granules opening to the cell surface. The presence of T6 antigen (CD1a) 30 min after tape-stripping, with loss of epidermal T6+ LCs and presence of T6+ LCs within the dermal blood vessels 24 h after tape-stripping, strongly suggest development of LCs’ migratory status, followed by amplification of the immune response 7 days after tape-stripping. Conclusion: Because BG contain both C-type lectin (langerin) and T6 antigen (CD1a), BG in activated LCs may provide a mechanism whereby presynthesized molecules (langerin, T6/CD1a, toll receptors) necessary for early LC activation and migration may be simultaneously delivered to the cell surface membrane for rapid enhancement of activated cell function by nonpeptide antigens.