CRL-1072 Enhances Antimycobacterial Activity of Human Macrophages Through Interleukin-8

Autor: Chinnaswamy Jagannath, Robert L. Hunter, Suresh Pai, Jeffrey K. Actor
Rok vydání: 1999
Předmět:
Zdroj: Journal of Interferon & Cytokine Research. 19:67-76
ISSN: 1557-7465
1079-9907
DOI: 10.1089/107999099314432
Popis: CRL-1072 is a poloxamer surfactant that kills mycobacteria more effectively within macrophages than in broth cultures. Human macrophages treated with CRL-1072 synthesized interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in a dose-dependent manner. About 3000 pg of IL-8 per million human macrophages accumulated in cultures treated with 100-1500 ng of poloxamer, with mRNA message for IL-8 induced as early as 2 h. As macrophages do not have IL-RA receptors, a transwell culture was used to study the chemotactic and activating effects of IL-8 between CRL-1072-treated human macrophage effectors and polymorphonuclear neutrophil (PMN) targets. PMN were activated by IL-8 and secreted hydrogen peroxide and myeloperoxidase (MPO). MPO derived from PMN, in turn, activated monocytes for an enhanced killing of intracellular Mycobacterium avium. The ability of CRL-1072 to modulate macrophage-mediated activation of neutrophils and receive a feedback activation signal may form one mechanism by which its antimycobacterial activity is achieved in vivo.
Databáze: OpenAIRE