MAST-CELL DEGRANULATION UP-REGULATES ALPHA-6-INTEGRINS ON EPIDERMAL LANGERHANS CELLS

The expression of the alpha6beta4 and alpha6beta1 integrins on epiderm al Langerhans cells (LC) before and after mast cell degranulation was studied in cultured human neonatal foreskin by immunohistochemistry. T wenty-four hours after addition of mast cell secretagogues, morphine s ulfate, or substance P, solitary mid-epidermal cells showed staining f or the integrin subunits alpha6, beta4, and beta1. This expression was not observed in cultured control explants, and immunostained cells we re confirmed to be non-epithelial, dendritic cells by immunoelectron m icroscopy. The identity of these cells as LC was further established b y coincident staining for alpha6 and CD1a using double immunofluoresce nce labeling. Addition of tumor necrosis factor-alpha (TNFalpha), the predominant cytokine in mast cell granules, also induced LC to express alpha6 integrins. Furthermore, preincubation of skin organ cultures w ith anti-TNFalpha antibodies or the mast cell inhibitor cromolyn sodiu m abrogated the ability to induce alpha6 integrins on LC consequent to experimental mast cell degranulation by substance P. These data impli cate a role for mast cell-derived TNFalpha in the regulation of the in tegrins alpha6beta4 and alpha6beta1 on LC. These findings may have imp ortant implications relevant to mechanisms for spatial localization of LC within the cutaneous compartments during immune responses.