Researchers Need Immunology Research Software To Track Mechanobiological Macrophage Signals

Designed to Cure

macrophage mediated pigment trafficking
Closeup of zebrafish pigmentation, which requires macrophage mediated pigment trafficking. Source: Wikipedia user Rockpocket.

Macrophages are known for their phagocytotic action and modest cytokine secretions in support of effector immune cells.1 Though a running joke among immunologists is that macrophages “do everything,” few would hazard that macrophages have mechanobiological activity in which they act as oversized vesicles. In a new paper exploring macrophages in zebrafish, researchers claim that they’ve discovered a novel functionality: mechanobiological pigment trafficking during postembryonic development.2 If researchers hope to understand mechanobiological transfer activities of macrophages, they’ll need to make use of a software platform which can handle tracking an entirely new class of data which researchers might not even have the right terms to quantify yet.

From Phagocytes to Pigment Formation

Zebrafish are transparent when young, but gain a single stripe of color as they mature. To gain that color, zebrafish have a complex pigmentation metabolism pathway which occurs far from the intended destination for the pigments, necessitating transport.3 Pigment distribution is a common task for animals, and there’s quite a bit of research which indicates a shared mechanism.4

Typically, researchers assumed that the pigments would be transported to the relevant sites on the zebrafish by vesicles. By investigating this pigment trafficking further, researchers found counterintuitive results. Confusingly, there’s some evidence that vesicles are necessary but not sufficient for proper pigment distribution, as researchers learned when they depleted macrophages in the zebrafish. In macrophage-depleted zebrafish, pigments were still carried by vesicles, but didn’t make it far enough to make a physiologically normal zebrafish. Instead, the zebrafish who grew under macrophage-depleted treatments exhibited blotched pigmentation rather than striped.  

By inferring that depletion of macrophages influenced pigment distribution, researchers were forced to describe an unknown mechanism that eventually became the topic of their paper. As it turns out, macrophages traffic pigments via a familiar mechanism: phagocytosis. What differs is what occurs after trafficking. In the paper, the researchers describe the phagocytosing of vesicles laden with pigments as the starting point of the macrophage’s role as mechanobiological ferry. At the endpoint, the researchers found that the macrophages’ direct contact with the intended pigment site was difficult to quantify, but clearly not mediated by vesicular activity.

Mechanobiological Mechanisms

Asserting that macrophages have mechanobiological activity isn’t so crazy, but it does entail a new way of thinking about them. Indeed, mechanobiological activity is neither purely vesicular, nor purely filopodial. Though macrophages are known to have filopodial projections, vesicular activity is somewhat different.5 Filopodial projections require utilizing large portions of membrane via actin filament polymerization, whereas vesicular budding does not.6 No single experimental intervention to date has explored whether pigment trafficking occurs differently when both filopodia and vesicles are inhibited.

Combining of these two traditional mechanisms is the proposed mechanism for macrophage pigment trafficking: microtubuole rails extended from filopodia which are used as tracks for vesicles to reach their final destination. Thus, the full picture of macrophage mechanobiology has three parts, representing a novel hypothesis as proposed by the new paper. This is important to note because the other two aforementioned mechanisms represent the extent of traditional knowledge regarding macrophage activity which might be responsible for pigment trafficking. Mechanobiology within macrophages is freshly broken ground as far as cellular biologists are concerned.

If researchers want to look for similar instances of this new pigment trafficking mechanism, they’ll need to figure out how to understand the new phenomena as a combination of old phenomena. In particular, learning more about macrophage mechanobiological activity will require the following:

  • Characterization of the final steps of pigment synthesis
  • Mechanism of localization of macrophages to the point of pigment synthesis
  • Characterizing the packaging of pigments before phagocytosis by the macrophage
  • Characterizing the “loaded” macrophage localization to the physiological pigment bearing site
  • Determining whether microtubuole formation inhibition prevents all pigment trafficking or merely changes the distribution
  • Determining whether vesicle formation inhibition prevents all pigment trafficking or merely changes the distribution
  • Determining whether filopodia inhibition permits viable macrophages when bearing pigments
  • Determining the genomic signals which differentiate between when macrophages use vesicles, filopodia, or the newly proposed mechanism with microtubuoles
  • Finding correlate mechanisms in other eukaryotes, and if present in humans, determining the health implications of variations in macrophage trafficking
Conquering Macrophage Mechanobiology

The intricacies of microtubuole formation, filopodia formation and vesicle formation are far from settled science. Though these mechanisms are heavily evolutionarily conserved, researchers have a lot of work to do if they’re looking to be the first to publish within this previously unexplored area of science. Research into the new mechanobiological activity of macrophages will be held to a higher standard, and researchers will have to produce a vast amount of data with each new publication. It’ll be all but impossible to publish to the standard required if researchers can’t bring the right data to bear.

It’s clear that the current standard of technology in laboratory software can’t keep up with the number of questions and the nature of data that will come out of mechanobiological mechanism research in macrophages. Like in many studies of pigmentation ontology, researchers made use of functional assays, pictures, videos, genetic information, metabolic information, and zebrafish physiological data. Likewise, while zebrafish work introduces a substantial amount of data to be collected, so do macrophages even before the introduction of a new data set. Far from being a simple data set, macrophages themselves necessitate a laboratory information platform that can keep up with their many functionalities and many types of data output.

Designed to Cure is the software platform that your laboratory will need to start exploring macrophage mechanobiology. Using Designed to Cure, you’ll be able to create and analyze diverse data sets, track new data generation, and collate prior literature to make your experiment planning easier. Contact us today to find out how we can help you flesh out undiscovered mechanisms within cellular biology and learn how macrophages influence human health in a new frontier.

  1. “Tumor Associated Macrophages and Neutrophils in Tumor Progression.” July 2013, https://www.ncbi.nlm.nih.gov/pubmed/23065796
  2. “A Macrophage Relay For Long-Distance Signaling During Postembryonic Tissue Remodeling.” February 2017, http://science.sciencemag.org/content/early/2017/02/15/science.aal2745
  3. “Small Molecule Screening Identifies Targetable Zebrafish Pigmentation Pathways.” February 2012, http://onlinelibrary.wiley.com/doi/10.1111/j.1755-148X.2012.00977.x/full
  4.  “Pigment Cell Mechanism Of Postembyonic Stripe Pattern Formation in the Japanese Four-Lined Snake.” February 2016, https://www.ncbi.nlm.nih.gov/pubmed/26589888
  5. “Macrophages Lift Off Surface-Bound Bacteria Using A Filopodium-Lamellipodium Hook-And-Shovel Mechanism.” June 2013, https://www.nature.com/articles/srep02884?WT.feed_name=subjects_lamellipodia
  6. “Direct Measurement Of Force Generation By Actin Filament Polymerization Using an Optical Trap.” 2007, http://chemport.cas.org/cgi-bin/sdcgi?APP=ftslink&action=reflink&origin=npg&version=1.0&coi=1:CAS:528:DC%2BD2sXisVWrsLo%3D&md5=3e163d4584b6a2f82d261b7c05f86561