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New Study Describes how Macrophages Mediate Tissue Remodeling



Review of “A macrophage relay for long-distance signaling during postembryonic tissue remodeling” from Science by Stuart P. Atkinson

The word macrophage derives from the Greek for “big eaters”, an apt moniker for immune cells whose major role is to recognize, engulf, and digest unwanted or foreign substances such as cell debris, microbes, and cancer cells. However, their utility also extends to processes related to development and homeostasis [1, 2]. Given this fact, researchers from the laboratories of Dae Seok Eom and David M. Parichy (University of Washington, Seattle, USA) have studied the consequences of macrophage loss during development to define any consequences in post-embryonic tissue remodeling. 

Their new Science study, using the zebrafish model animal, now suggests that non-immune cells employ macrophages to actively promote tissue remodeling in what may represent an important new mechanism controlling development and a new means to artificially control tissue regeneration [3].

Specifically, the authors determined that depletion of macrophages during zebrafish development disrupted the formation of the expected adult color patterning, a similar finding to a previous study assessing defects to long-distance communication between color-bearing cell precursors [4]. Following detailed analysis employing various cell-specific reporter constructs, the authors discovered that the presence of macrophages promoted the extension of thin cellular projections (airinemes) by dragging cell surface components from yellow-color progenitor cells in order to make contacts with black/brown-color progenitor cells. These data suggested that macrophages aid long-distance cellular communication between color-producing cells during development to promote tissue remodeling and produce adult specific patterns.

But just what controls macrophage-mediated airineme extension? On the surface of apoptotic cells, the phospholipid phosphatidylserine (PS) appears and “entices” macrophages to make contact and begin the cellular removal process [5]. However, in the developing zebrafish, the yellow color-cell progenitors exploited the PS system to lure macrophages into making contact and permitting airineme extension. 

We still know little about this long-range tissue-remodeling mechanism, but the authors propose that further studies may shed light on the evolution and generality of this system and even open the door to use this “macrophage-relay” as a novel means to artificially stimulate tissue remodeling or deliver therapeutic agents.

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  1. Stefater JA, 3rd, Ren S, Lang RA, et al. Metchnikoff's policemen: macrophages in development, homeostasis and regeneration. Trends Mol Med 2011;17:743-752.
  2. Wynn TA, Chawla A, and Pollard JW. Macrophage biology in development, homeostasis and disease. Nature 2013;496:445-455.
  3. Eom DS and Parichy DM. A macrophage relay for long-distance signaling during postembryonic tissue remodeling. Science 2017;355:1317-1320.
  4. Eom DS, Bain EJ, Patterson LB, et al. Long-distance communication by specialized cellular projections during pigment pattern development and evolution. Elife 2015;4:
  5. Hochreiter-Hufford A and Ravichandran KS. Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion. Cold Spring Harb Perspect Biol 2013;5:a008748.