BIOSYNTHESIS, PROCESSING AND SORTING OF NEUTROPHIL PROTEINS - INSIGHTINTO NEUTROPHIL GRANULE DEVELOPMENT

Neutrophil granulocytes are specialized phagocytic cells that carry a collection of granules for regulated secretion, each with distinct con stituents. The granules can be classified as azurophil (primary), deve loped first, followed in time by specific (secondary) granules gelatin ase granules, and secretory vesicles. Stage- and tissue-specific trans cription factors govern the successive expression of genes for granule proteins to allow storage of the gene products in these organelle cat egories whose packaging is separated in time. Many of the granule prot eins, in particular those of the heterogeneous lysosome-like azurophil granules, are subject to extensive post-translational proteolytic pro cessing into mature proteins, most commonly as a post-sorting event. A selective aggregation of proteins destined for storage in granules, a s discussed in this review, would facilitate their retention and elimi nate a need for distinct sorting motifs on each granule protein. Aggre gation of granule proteins, that are often cationic, would be assisted by the anionic serglycin proteoglycans present in neutrophils. The an tibacterial granule proteins can serve as models for antibiotics and s ome of them possess a potentially useful therapeutic ability to bind a nd neutralize endotoxin. Because aberrant expression of transcription factors regulating the synthesis of granule proteins is often found in leukemia, the clarification of mechanisms regulating the timed expres sion of granule proteins will shed light on the maturation block in my eloid leukemias.