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Review
. 2014 Oct 27:5:538.
doi: 10.3389/fimmu.2014.00538. eCollection 2014.

Cytokine Secretion in Macrophages: SNAREs, Rabs, and Membrane Trafficking

Rachael Zoe Murray  1 , Jennifer Lea Stow  2
Affiliations
Review

Cytokine Secretion in Macrophages: SNAREs, Rabs, and Membrane Trafficking

Rachael Zoe Murray et al. Front Immunol. .

Abstract

Macrophages have the capacity to rapidly secrete a wide range of inflammatory mediators that influence the development and extent of an inflammatory response. Newly synthesized and/or preformed stored cytokines and other inflammatory mediators are released upon stimulation, the timing, and volume of which is highly regulated. To finely tune this process, secretion is regulated at many levels; at the level of transcription and translation and post-translationally at the endoplasmic reticulum (ER), Golgi, and at or near the cell surface. Here, we discuss recent advances in deciphering these cytokine pathways in macrophages, focusing on recent discoveries regarding the cellular machinery and mechanisms implicated in the synthesis, trafficking, and secretion of cytokines. The specific roles of trafficking machinery including chaperones, GTPases, cytoskeletal proteins, and SNARE membrane fusion proteins will be discussed.

Keywords: IL-10; IL-6; Rabs; SNAREs; TNF; cytokine secretion; macrophages.

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Figures

Figure 1
Figure 1
Classical transport pathways used to secrete macrophage cytokines. Three major transport pathways for cytokine secretion have been identified to date. The first involves direct transport to the cell surface (IL-10) from the TGN, the second pathways routes cytokines via the recycling endosome and the out to the cell surface (TNF, IL-6, and IL-10), and the 3rd pathway occurs during phagocytosis where cytokine (TNF) is routed from the recycling endosome to the phagocytic cup.
Figure 2
Figure 2
Trafficking machinery regulating specific cytokine transport steps in macrophages is shown. The transport machinery that regulates the three major transport steps is shown.
Figure 3
Figure 3
Schematic showing the basic steps in SNARE-mediated secretion is shown. An R-SNARE on the donor membrane comes together with a Q-SNARE complex, consisting of two to three Q-SNAREs, on the target membrane to form a trans-SNARE complex. This brings the two membranes into close proximity leading to the formation of a fusion pore allowing the release of some or all of the contents of the vesicle. The pore can either close (“kiss and run”) or as depicted above the membrane can fully fuse thus incorporating all of its membrane-associated proteins into the target membrane. This basic process is same in all cell types and at different stages of the transport pathways. What differs is the precise SNARE partners at these distinct stages.
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