Compartmentalization of PDE-4 and cAMP-dependent protein kinase in neutrophils and macrophages during phagocytosis.

The compartmentalization of cAMP in human neutrophils during phagocytosis of serum-opsonized zymosan suggests that cAMP is an important second messenger for regulating phagocytosis. Type 4 cAMP-specific phosphodiesterase (PDE-4), cAMP-dependent protein kinase (PKA), and adenylate cyclase are the principal effector molecules for cAMP regulation in phagocytes. Immunofluorescence microscopy demonstrated that PDE-4 isoforms (HSPDE-4A, HSPDE-4B, HSPDE-4D) were targeted to the forming phagosome in neutrophils, and were colocalized with the catalytic subunit of PKA and degranulated myeloperoxidase.

Localization of cyclic GMP-dependent protein kinase in human mononuclear phagocytes.

The presence and physiological role of cGMP-dependent protein kinase (G-kinase) was investigated in human mononuclear phagocytes. Western blots of monocyte extracts revealed a single polypeptide band that comigrated with purified bovine lung G-kinase. G-kinase was localized by immunofluorescence microscopy in freshly isolated adherent human monocytes, monocyte-derived macrophages cultured from 4 to 14 days, and alveolar macrophages.

Regulation of tumour necrosis factor-alpha processing by a metalloproteinase inhibitor.

Tumour necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory agent produced primarily by activated monocytes and macrophages. TNF-alpha is synthesized as a precursor protein of M(r) 26,000 (26K) which is processed to a secreted 17K mature form by cleavage of an Ala-Val bond between residues 76-77. The enzyme(s) responsible for processing pro-TNF-alpha has yet to be identified.

RRR-alpha-tocopheryl succinate induced interleukin-2 production by avian splenic T lymphocytes and murine EL-4 thymic lymphoma cells.

RRR-alpha-tocopheryl succinate (vitamin E succinate) was studied for its effects on interleukin-2 (IL-2) production by chicken splenic derived T lymphocytes and murine EL-4 thymic lymphoma cells. Supernatants from 0.1 microgram/mL vitamin E succinate-supplemented chicken splenic T cell cultures exhibited 42-72% enhanced IL-2 production over vehicle controls when tested in a chicken T cell blast bioassay.

Effects of RRR-alpha-tocopheryl succinate on IL-1 and PGE2 production by macrophages.

Vitamin E is thought to enhance immunity by increasing interleukin-1 (IL-1) production and by downregulating prostaglandin E2 (PGE2) synthesis. In an effort to understand the mechanism(s) whereby the form of vitamin E known as RRR-alpha-tocopheryl succinate [also called vitamin E succinate (VES)] ameliorates retrovirus-induced immune dysfunctions, peritoneal exudate cells (PECs) derived from normal chickens and avian and murine macrophage cell lines were used as in vitro model systems to test the effects of VES treatments on PGE2 and IL-1 production. Supernatants from PECs that were exposed to avian erythroblastosis virus (AEV) for 45 minutes exhibited a 256% increase in PGE2 levels compared with supernatants from replica cultures of PECs not exposed to AEV.