Neutrophils overcome their ability to cluster by synergistic production of LTB4 across cellular biosynthesis

Neutrophils require lipid mediator leukotriene B4 (LTB4) aggregation in response to fungal targets
.
LTB4 is synthesized by neutrophils upon aggregation
.

Since colony behavior is a collective behavior, we sought to determine whether neutrophils can generate this mediator by cooperating across cellular biosynthetic mechanisms, and whether this process can save defective colony behavior
in mutant cells that are unable to synthesize LTB4.
We employ in vitro platforms for neutrophil clusters, including microfluidics, genetically deficient mouse cells, and targeted metabolomics analysis
.
Neutrophils with mutations were found to be unable to synthesize lipid signaling (LTB4) and could not aggregate
.
If you mix two neutrophil populations, each with a different LTB4 synthetase removed, the cells in the mixture will cooperate across cellular biosynthesis to produce LTB4, overcoming their inability
to aggregate.
With a better understanding of the mechanisms that drive neutrophil clusters, this critical inflammatory function could therapeutically better control the infectious response or potentially damaging autoinflammatory processes
.

Transcellular biosynthesis of leukotriene B4 orchestrates neutrophil swarming to fungi