Papain, found naturally in papaya and ioften referred to as a “plant-based pepsin”, is an important industrial protein-degrading enzyme for the food and cosmetic industries. The cosmetic industry uses papain in exfoliating treatments to remove dead surface skin and there even are enzyme-based shampoos for house pets to clean the fur and make it easier to brush. 

But lots of natural things can trigger allergic reactions. 

Skin consists of several layers joined via cellular connections called “tight junctions”. In a new study, the authors showed that papain induces a breakdown of these cell-cell junctions. On the skin, papain results in a loss of the barrier function. That is why when humans or animals come in contact with papain, strong allergic reactions of the skin can be the result. The new work researched the effect of papain directly on the skin of mice as well as on skin cells in the petri dish. 

“After just a short period of time, papain increased vascular permeability and inflammatory cells infiltrated the skin,” says Erika Jensen-Jarolim, Head of the Department of Comparative Medicine at the Messerli Research Institute.

Around two weeks after being exposed to papain, the researchers found antibodies to papain in the mice. These immunoglobulins are the cause of the allergic reaction toward the enzyme.

“Exposed mice not only experienced a loss of the barrier function of the skin, but also had a specific allergic sensitization toward papain. The animals developed an allergy,” says Jensen-Jarolim.

But the permeation of the skin barrier does not appear to be a prerequisite for sensitization toward papain.

“The enzyme remains allergenic even when its enzymatic function has been blocked,” explains Jensen-Jarolim. The disruption to the skin barrier, she says, is essential for the infiltration of other allergens and bacteria. In humans and in animals, diseases of the skin such as atopic dermatitis, commonly referred to as eczema, involve an increased permeability of the skin with a heightened risk for bacterial, fungal, or viral colonization. Besides genetic factors, allergenic enzymes from external sources may also contribute to the symptoms.

It is striking that papain has an enormous structural similarity with one of the most important house dust mite allergens. The authors conclude that sensitization toward these house dust mite allergens follows the same principle. 

Citation: Caroline Stremnitzer, Krisztina Manzano-Szalai, Anna Willensdorfer, Philipp Starkl, Mario Pieper, Peter König, Michael Mildner, Erwin Tschachler, Ursula Reichart and Erika Jensen-Jarolim, “Papain Degrades Tight Junction Proteins of Human Keratinocytes In Vitro and Sensitizes C57BL/6 Mice via the Skin Independent of its Enzymatic Activity or TLR4 Activation” Journal of Investigative Dermatology.