DIFFERENTIAL EXPRESSION OF GRO-ALPHA AND IL-8 MESSENGER-RNA IN PSORIASIS - A MODEL FOR NEUTROPHIL MIGRATION AND ACCUMULATION IN-VIVO

Dense focal accumulation of neutrophils in the upper epidermis is a ha llmark of psoriasis, Because the signals for neutrophil diapedesis and migration in vivo are not fully understood, psoriatic lesions with pr onounced migration of neutrophils may serve as an important model for studying neutrophil chemotaxis, In this study, we present evidence for differential expression of the neutrophil chemotactic cytokines growt h-related oncogene alpha, interleukin-8, and ENA-78 (epithelial cell d erived and neutrophil-activating properties, 78 amino acids) in psoria tic lesions, In situ hybridization and immunohistochemistry of serial sections were employed to identify and microanatomically localize the cells producing these chemokines, High levels of focal interleukin-8 m essage were found to be expressed in the upper epidermis by keratinocy tes and, most importantly, neutrophils themselves, Growth-related onco gene alpha transcripts were detected in clusters of keratinocytes of t he upper epidermis at the same sites where interleukin-8 mRNA was abun dant. In contrast to interleukin-8, growth-related oncogene alpha was also detected in the papillary dermis produced by vessel-associated ce lls, Sites of interleukin-8 and growth-related oncogene alpha mRNA exp ression were associated with infiltration of neutrophils, Interestingl y, mRNA expression of the highly homologous chemokine ENA-78 was quies cent. In conclusion, our data indicate that growth-related oncogene al pha is an important chemoattractant for neutrophil diapedesis ill vivo , whereas further migration of neutrophils and formation of micropustu les appears to be influenced by the cooperative action of both growth- related oncogene alpha and interleukin-8.