Cytokine secretion in macrophages and other cells: pathways and mediators

Jennifer L Stow1, Pei Ching Low, Carolin Offenhäuser

  • 1Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia. j.stow@imb.uq.edu.au

Immunobiology
|March 10, 2009
PubMed

Insights

Immune cells release cytokines through various intracellular pathways, including novel routes via recycling endosomes. Understanding these cytokine trafficking mechanisms is crucial for regulating immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Immune cells secrete cytokines and immune mediators for cell communication during immune responses.
  • While cytokine functions are known, their intracellular secretion pathways are not fully understood.
  • Cytokine release occurs via secretory granules or constitutive secretory pathways with dynamic vesicular carriers.

Purpose of the Study:

  • To describe and exemplify intracellular pathways for cytokine trafficking and release in macrophages.
  • To identify the cellular machinery involved in cytokine transport.
  • To highlight the regulatory roles of trafficking pathways in immune responses.

Main Methods:

  • Microscopy and biochemical assays to visualize and analyze cytokine transport.
  • Genetic manipulation to identify key cellular machinery.
  • Macrophage cell culture models.

Main Results:

  • Newly synthesized cytokines can be routed through compartments like recycling endosomes before secretion.
  • Specific cellular machinery, including vesicular carriers, is required for dynamic cytokine transport.
  • Macrophages utilize diverse pathways for cytokine release, differing from traditional models.

Conclusions:

  • Intracellular trafficking pathways play significant regulatory roles in immune responses.
  • Detailed understanding of cytokine secretion mechanisms is essential for manipulating immune cell function.
  • Further research into these pathways can reveal new therapeutic targets for immune-related diseases.

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Differentiation of Common Myeloid Progenitor Cells01:15

Differentiation of Common Myeloid Progenitor Cells

Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...