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 the CXC chemokines and acts as a potent chemoattractant and activator of neutrophil function. On stimulation in vitro, ENA-78 is highly expressed 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 recognized as a major CXC chemokine expressed in epithelial cells of the intestinal mucosa of patients with Crohn's disease, ulcerative colitis, and acute appendicitis. A high expression of ENA-78 and interleukin-8 (IL-8) was also observed in the exocrine tissue of patients with chronic pancreatitis (CP). It is interesting to note that expression of IP-10, MIP-1 alpha, and MCP-1 is high in healthy pancreatic tissue but low in tissue of patients with CP, suggesting a mutually exclusive expression of the ELR-CXC vs. non-ELR-CXC/CC chemokines. High-resolution studies of intracellular chemokines has revealed specific immunoreactivity for ENA-78 associated with the endoplasmic reticulum of many cell types. In contrast, GRO alpha immunoreactivity was exclusively localized in the nucleus. Despite their common effects on neutrophil functions, the differential intracellular localization of ENA-78 and GRO alpha suggests additional roles for these two chemokines in normal cell biology.