Mast cell degranulation upregulates α6 integrins on epidermal langerhans cells

The expression of the α6β4 and α6β1 integrins on epidermal Langerhans cells (LC) before and after mast cell degranulation was studied in cultured human neonatal foreskin by immunohistochemistry. Twenty-four hours after addition of mast cell secretagogues, morphine sulfate, or substance P, solitary mid-epidermal cells showed staining for the integrin subunits α6, β4, and β1. This expression was not observed in cultured control explants, and immunostained cells were confirmed to be non-epithelial, dendritic cells by immunoelectron microscopy. The identity of these cells as LC was further established by coincident staining for α6 and CD1a using double immunofluorescence labeling. Addition of tumor necrosis factor-α (TNFα), the predominant cytokine in mast cell granules, also induced LC to express of α6 integrins. Furthermore, preincubation of skin organ cultures with anti-TNFα antibodies or the mast cell inhibitor cromolyn sodium abrogated the ability to induce α6 integrins on LC consequent to experimental mast cell degranulation by substance P. These data implicate a role for mast cell-derived TNFα in the regulation of the integrins α6β4 and α6β1 on LC. These findings may have important implications relevant to mechanisms for spatial localization of LC within the cutaneous compartments during immune responses.