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Macrophage heterogeneity in tissues: phenotypic diversity and functions.

Gordon S, Plüddemann A, Martinez Estrada F - Immunol. Rev. (2014)

Bottom Line: During development and throughout adult life, macrophages derived from hematopoietic progenitors are seeded throughout the body, initially in the absence of inflammatory and infectious stimuli as tissue-resident cells, with enhanced recruitment, activation, and local proliferation following injury and pathologic insults.We have learned a great deal about macrophage properties ex vivo and in cell culture, but their phenotypic heterogeneity within different tissue microenvironments remains poorly characterized, although it contributes significantly to maintaining local and systemic homeostasis, pathogenesis, and possible treatment.In this review, we summarize the nature, functions, and interactions of tissue macrophage populations within their microenvironment and suggest questions for further investigation.

View Article: PubMed Central - PubMed

Affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

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Heterogeneity of F4/80+ cells in adult mouse brain. F4/80+ microglia are present in large numbers in all major divisions of the brain but are not uniformly distributed. There is a more than fivefold variation in the density of immunostained microglial processes between different regions. More microglia are found in gray matter than white. Microglia vary in morphology depending on their location. Compact cells are rounded, sometimes with one or two short thick limbs, bearing short processes. They resemble Kupffer cells of the liver and are found exclusively in sites lacking a blood–brain barrier. Longitudinally branched cells are found in fiber tracts and possess several long processes which are usually aligned parallel to the longitudinal axis of the nerve fibers. Radially branched cells are found throughout the neuropil. They can be extremely elaborate and there is wide variation in the length and complexity of branching of the processes. The systematic variation in microglial morphology provides evidence that these cells are sensitive to their microenvironment. Drawings to illustrate the morphological heterogeneity of macrophage populations of the central nervous system: A,C,D show microglia of the brain parenchyma (A, cortex; B, white matter; C, ventral pallidum). Macrophages with a simpler morphology are also present in the circumventricular organs (B), the meninges (E), and choroid plexus (F). Based on 106 which should be consulted for further details. Image courtesy of L. J. Lawson and V. H. Perry.
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fig03: Heterogeneity of F4/80+ cells in adult mouse brain. F4/80+ microglia are present in large numbers in all major divisions of the brain but are not uniformly distributed. There is a more than fivefold variation in the density of immunostained microglial processes between different regions. More microglia are found in gray matter than white. Microglia vary in morphology depending on their location. Compact cells are rounded, sometimes with one or two short thick limbs, bearing short processes. They resemble Kupffer cells of the liver and are found exclusively in sites lacking a blood–brain barrier. Longitudinally branched cells are found in fiber tracts and possess several long processes which are usually aligned parallel to the longitudinal axis of the nerve fibers. Radially branched cells are found throughout the neuropil. They can be extremely elaborate and there is wide variation in the length and complexity of branching of the processes. The systematic variation in microglial morphology provides evidence that these cells are sensitive to their microenvironment. Drawings to illustrate the morphological heterogeneity of macrophage populations of the central nervous system: A,C,D show microglia of the brain parenchyma (A, cortex; B, white matter; C, ventral pallidum). Macrophages with a simpler morphology are also present in the circumventricular organs (B), the meninges (E), and choroid plexus (F). Based on 106 which should be consulted for further details. Image courtesy of L. J. Lawson and V. H. Perry.

Mentions: A similar strategy was used to investigate macrophage adhesion, providing reagents to probe cell recruitment (CD11b) and scavenger receptor A (SR-A)-mediated endocytosis. Specific monoclonal antibodies were generated for previously described lectin-like receptors, such as the Mannose receptor, CD206. Table 1 summarizes the properties and expression of a range of these and related reagents. Application of this panel of reagents revealed striking heterogeneity between different tissue macrophages, e.g. in liver and mouse spleen (Figs 1and2), but also within individual organs such as the brain (Fig. 3).


Macrophage heterogeneity in tissues: phenotypic diversity and functions.

Gordon S, Plüddemann A, Martinez Estrada F - Immunol. Rev. (2014)

Heterogeneity of F4/80+ cells in adult mouse brain. F4/80+ microglia are present in large numbers in all major divisions of the brain but are not uniformly distributed. There is a more than fivefold variation in the density of immunostained microglial processes between different regions. More microglia are found in gray matter than white. Microglia vary in morphology depending on their location. Compact cells are rounded, sometimes with one or two short thick limbs, bearing short processes. They resemble Kupffer cells of the liver and are found exclusively in sites lacking a blood–brain barrier. Longitudinally branched cells are found in fiber tracts and possess several long processes which are usually aligned parallel to the longitudinal axis of the nerve fibers. Radially branched cells are found throughout the neuropil. They can be extremely elaborate and there is wide variation in the length and complexity of branching of the processes. The systematic variation in microglial morphology provides evidence that these cells are sensitive to their microenvironment. Drawings to illustrate the morphological heterogeneity of macrophage populations of the central nervous system: A,C,D show microglia of the brain parenchyma (A, cortex; B, white matter; C, ventral pallidum). Macrophages with a simpler morphology are also present in the circumventricular organs (B), the meninges (E), and choroid plexus (F). Based on 106 which should be consulted for further details. Image courtesy of L. J. Lawson and V. H. Perry.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231239&req=5

fig03: Heterogeneity of F4/80+ cells in adult mouse brain. F4/80+ microglia are present in large numbers in all major divisions of the brain but are not uniformly distributed. There is a more than fivefold variation in the density of immunostained microglial processes between different regions. More microglia are found in gray matter than white. Microglia vary in morphology depending on their location. Compact cells are rounded, sometimes with one or two short thick limbs, bearing short processes. They resemble Kupffer cells of the liver and are found exclusively in sites lacking a blood–brain barrier. Longitudinally branched cells are found in fiber tracts and possess several long processes which are usually aligned parallel to the longitudinal axis of the nerve fibers. Radially branched cells are found throughout the neuropil. They can be extremely elaborate and there is wide variation in the length and complexity of branching of the processes. The systematic variation in microglial morphology provides evidence that these cells are sensitive to their microenvironment. Drawings to illustrate the morphological heterogeneity of macrophage populations of the central nervous system: A,C,D show microglia of the brain parenchyma (A, cortex; B, white matter; C, ventral pallidum). Macrophages with a simpler morphology are also present in the circumventricular organs (B), the meninges (E), and choroid plexus (F). Based on 106 which should be consulted for further details. Image courtesy of L. J. Lawson and V. H. Perry.
Mentions: A similar strategy was used to investigate macrophage adhesion, providing reagents to probe cell recruitment (CD11b) and scavenger receptor A (SR-A)-mediated endocytosis. Specific monoclonal antibodies were generated for previously described lectin-like receptors, such as the Mannose receptor, CD206. Table 1 summarizes the properties and expression of a range of these and related reagents. Application of this panel of reagents revealed striking heterogeneity between different tissue macrophages, e.g. in liver and mouse spleen (Figs 1and2), but also within individual organs such as the brain (Fig. 3).

Bottom Line: During development and throughout adult life, macrophages derived from hematopoietic progenitors are seeded throughout the body, initially in the absence of inflammatory and infectious stimuli as tissue-resident cells, with enhanced recruitment, activation, and local proliferation following injury and pathologic insults.We have learned a great deal about macrophage properties ex vivo and in cell culture, but their phenotypic heterogeneity within different tissue microenvironments remains poorly characterized, although it contributes significantly to maintaining local and systemic homeostasis, pathogenesis, and possible treatment.In this review, we summarize the nature, functions, and interactions of tissue macrophage populations within their microenvironment and suggest questions for further investigation.

View Article: PubMed Central - PubMed

Affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

Show MeSH
Related in: MedlinePlus