FUNCTIONAL CHEMOTACTIC FACTOR CP-10 AND MRP-14 ARE ABUNDANT IN MURINEABSCESSES

Murine abscesses induced by intraperitoneal injection of a mixture of Escherichia coli, Bacteroides fragilis, and bran are established model s for the study of localized infectious and inflammatory lesions. Chem otactic factors are thought to mediate the directed migration of large numbers of leukocytes into the abscess. Microorganisms located within the encapsulated lesion are not readily eliminated by the leukocytes, but their numbers are controlled over many weeks. We report the prese nce of large amounts of two murine S100 proteins, CP-10 and migration inhibition factor-related protein 14 (MRP-14), in abscesses as demonst rated by immunohistochemistry and measured by enzyme-linked immunosorb ent assay and Western blotting (immunoblotting), High levels of CP-10 (7.7 +/- 1 mg/ml) and MRP-14 (5.5 +/- 1 mg/ml) were found throughout t he time course of abscess development from early acute-phase lesions, which are predominantly neutrophilic, to late chronic-phase lesions, w hich contained more mononuclear cells, Approximately one-third of thes e amounts occurred as monomers (2.0 mg/ml for MRP 14 and 2.2 mg/ml for CP-10), Abscess fluid was strongly chemotactic, and a portion of the activity was due to CP-10, indicating its important role in leukocyte recruitment, CP-10-MRP-14 complexes were present in abscess fluid, and the proteins were immunoabsorbed together. In analogy with the relate d human MRP-8-MRP-14 complex, these proteins could be involved in the inhibition of microbial growth. No growth inhibition occurred with 20 mu g of CP-10 or MRP-14 per ml or with mixtures of both, but these con centrations may have been insufficient and were not representative of the high concentrations found within abscesses, CP-10 may contribute i ndirectly to the antimicrobial response in abscesses by virtue of its strong chemotactic. properties and its capacity to modulate the activa tion state of recruited leukocytes.