| Over the last decade, reports of immediate reactions to natural rubber latex products have been increasing dramatically worldwide. Latex proteins, ranging from 2--100+ kDa, have been identified as the antigens responsible for the IgE-mediated reactions. Although much data have been generated on the elicitation of latex allergies, less is known about how individuals become sensitized to NRL proteins. Exposure to latex proteins occurs mainly through the lungs, mucous membranes, and the skin. As a result, major efforts to reduce respiratory and mucosal exposure are beginning to be implemented worldwide. As large molecular weight proteins are generally considered unable to cross the skin barrier, little research has focused on the dermal exposure route in the development of latex protein sensitization. To begin elucidating the skin's role in latex protein allergy, we assembled and validated an in vitro percutaneous penetration model. Using this model, we investigated percutaneous penetration of 125I-labeled latex proteins using excised skin. The results demonstrated latex protein mixtures and one purified latex protein (hev b 6) can penetrate into and through both human and hairless guinea pig skin with compromised skin allowing a significant increase in percutaneous penetration. Immunohistochemistry localized the latex proteins in both the epidermal and dermal layers of the skin and select proteins that penetrated completely through the skin were visualized using electrophoresis and phosphoimaging techniques. A hairless guinea pig in vivo model was then used to evaluate the potential for latex sensitization following topical exposure to the same quantity of latex proteins used in the in vitro penetration studies. In as little as three months, an elevation of anti-latex antibodies was demonstrated in 20% of the animals. Taken together, these data demonstrate the skin is not only a plausible route for NRL sensitization, but can be a major exposure route when the integument has been compromised. |
