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American Journal of Pathology, Vol 135, 1045-1053, Copyright © 1989 by American Society for Investigative Pathology

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Keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression precedes dermal T lymphocytic infiltration in allergic contact dermatitis (Rhus dermatitis)

CE Griffiths and BJ Nickoloff
Department of Dermatology, University of Michigan Medical School, Ann Arbor.

The ability of small molecules such as urushiol, present as a wax on the poison ivy leaf surface, to cause allergic contact dermatitis (rhus dermatitis) has fascinated immunologists for decades. Current dogma suggests that these epicutaneously applied catechol-containing molecules serve as haptens to conjugate with larger proteins via reactive o-quinone intermediates. These complexes are then recognized as foreign antigens by the immune system and elicit a hypersensitivity reaction. Phorbol ester can directly induce cultured keratinocyte (KC) intercellular adhesion molecule-1 (ICAM-1) expression via a protein kinase C (PK-C)-dependent mechanism. As urushiol is also a known PK-C agonist, we asked if topical application of a poison ivy/oak mixture could directly induce epidermal KC ICAM-1 expression. During the pre- erythematous phase of this reaction (4 to 20 hours), epidermal KCs expressed ICAM-1; this "initiation phase" preceded the appearance of activated memory T lymphocytes in the papillary dermis, and thus appeared to be nonlymphokine mediated. A near-contiguous cellular- adhesion molecular network was identified by ICAM-1 staining of basal KCs, dermal dendrocytes, and endothelial cells. During the second 24- hour period with the onset of erythema and edema, there was an "amplification phase" of more intense KC ICAM-1 expression coupled with relatively weak KC HLA-DR expression that coincided with dermal and epidermal T-cell infiltration. This suggests the presence of lymphokines, such as gamma interferon, during the amplification phase because of KC HLA-DR expression. On cultured KCs, urushiol directly induced ICAM-1 expression but not HLA-DR. Thus, in addition to functioning as an antigenic hapten, urushiol directly induces KC ICAM-1 expression. The KC ICAM-1 expression may then alter the dynamic trafficking of memory T cells in the epidermis, so as to initiate cutaneous inflammation in a nonantigen specific manner. This initiation phase is followed by T-cell infiltration and consequent lymphokine production that significantly amplifies the original stimulus. Thus much can still be learned about the molecular pathophysiology of this common type of cutaneous inflammation.

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