REGULATION AND FUNCTION OF THE CXC CHEMOKINE ENA-78 IN MONOCYTES AND ITS ROLE IN DISEASE

Epithelial neutrophil-activating protein 78 (ENA-78) is a member of th e CXC chemokines and acts as a potent chemoattractant and activator of neutrophil function. On stimulation in vitro, ENA-78 is highly expres sed in many cell types. ENA-78 protein levels are strongly elevated in synovial fluid and blood of patients with rheumatoid arthritis. By in situ hybridization and immunofluorescence staining, ENA-78 has been r ecognized as a major CXC chemokine expressed in epithelial cells of th e intestinal mucosa of patients with Crohn's disease, ulcerative colit is, and acute appendicitis. A high expression of ENA-78 and interleuki n-8 (IL-8) was also observed in the exocrine tissue of patients with c hronic pancreatitis (CP). It is interesting to note that expression of IP-10, MIP-1 alpha, and MCP-1 is high in healthy pancreatic tissue bu t low in tissue of patients with CP, suggesting a mutually exclusive e xpression of the ELR-CXC vs. non-ELR-CXC/CC chemokines. High-resolutio n studies of intracellular chemokines has revealed specific immunoreac tivity for ENA-78 associated with the endoplasmic reticulum of many ce ll types. In contrast, GRO alpha immunoreactivity was exclusively loca lized in the nucleus. Despite their common effects on neutrophil funct ions, the differential intracellular localization of ENA-78 and GRO al pha suggests additional roles for these two chemokines in normal cell biology.