Immunity system complexity: macrophage spread (Introduction)

by David Turell , Saturday, April 23, 2022, 19:47 (944 days ago) @ David Turell

By cell division:

https://www.sciencemagazinedigital.org/sciencemagazine/22_april_2022_Main/MobilePagedAr...

"Cells migrate through crowded microenvironments within tissues during normal development, immune response, and cancer metastasis. Although migration through pores and tracks in the extracellular matrix (ECM) has been well studied, little is known about cellular traversal into confining cell-dense tissues. We find that embryonic tissue invasion by Drosophila macrophages requires division of an epithelial ectodermal cell at the site of entry. Dividing ectodermal cells disassemble ECM attachment formed by integrin-mediated focal adhesions next to mesodermal cells, allowing macrophages to move their nuclei ahead and invade between two immediately adjacent tissues. Invasion efficiency depends on division frequency, but reduction of adhesion strength allows macrophage entry independently of division. This work demonstrates that tissue dynamics can regulate cellular infiltration.

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"Macrophages are scavenger cells that invade tissues early on in development to establish residency and patrol organs (Display footnote number... This first macrophage requires ∼20 min to enter through the tissue barrier, using αPS2- and βPS-integrins that bind to laminin. Matrix metalloproteolytic ECM degradation does not affect the efficiency of entry (Display footnote number:10) but macrophage-specific programs do. How the dynamics and properties of surrounding cells influence macrophage tissue invasion remains unclear.

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"We have pinpointed surrounding tissue division as the crucial variable affecting the rate of entry of the first Drosophila macrophage. Vertebrate mitosis also leads to diminishment of focal adhesions. Our findings suggest that regulation of division during development, inflammation, or tumor growth could affect the number and placement of immune cells in tissues in a wide range of normal and disease contexts."

Comment: Macrophages. as front-line direct killers, must be spread throughout the embryo as it develops. Another example of careful design.