DEPOSITION OF EOSINOPHIL GRANULE PROTEINS PRECEDES BLISTER FORMATION IN BULLOUS PEMPHIGOID - COMPARISON WITH NEUTROPHIL AND MAST-CELL GRANULE PROTEINS

Eosinophils, neutrophils, and mast cells have all been implicated in t he pathogenesis of bullous pemphigoid (BP). To comparatively character ize the involvement of these cells in BP, 10 lesional skin biopsy spec imens were identified retrospectively and studied for tissue localizat ion of eosinophil, neutrophil, and mast cell granule proteins. Subsequ ently, multiple skin biopsies of lesions in various developmental stag es were obtained from 3 patients with untreated BP. Involved and uninv olved skin specimens were also obtained from 2 patients. Using indirec t immunofluorescence, retrospectively identified lesions showed eosino phils and extracellular granule protein deposition prominently in area s of blistering. Evolving lesions showed eosinophil granule protein de position in all stages but was most marked in early erythematous and p rebullous (urticarial) lesions and was minimal in uninvolved skin. Vas cular cell adhesion molecule-1, E-selectin, and P-selectin were detect ed on vessels and very late activation antigen-4 was detected on monon uclear cells and eosinophils by immunoperoxidase staining of lesions. Eosinophil granule proteins were increased in the peripheral blood, ur ine, and blister fluid. Blister fluids caused increased eosinophil sur vival that was inhibited by antibodies to interleukin-5 and interleuki n-3. Although neutrophil and mast cell infiltration was observed extra cellular granule protein deposition from these cells was minimal excep t in two specimens. These results demonstrate that eosinophils infiltr ate and deposit granule proteins early ia the development of BP lesion s, that eosinophil-activating cytokines are present in blister fluid, and that eosinophil-selective adhesion molecules are present. These st udies strongly support a role for eosinophils in blister formation in BP.