The role of the LTB4-BLT1 axis in chemotactic gradient sensing and directed leukocyte migration

Abstract

Directed leukocyte migration is a hallmark of inflammatory immune responses. Leukotrienes are derived from arachidonic acid and represent a class of potent lipid mediators of leukocyte migration. In this review, we summarize the essential steps leading to the production of LTB₄ in leukocytes. We discuss the recent findings on the exosomal packaging and transport of LTB₄ in the context of chemotactic gradients formation and regulation of leukocyte recruitment. We also discuss the dynamic roles of the LTB₄ receptors, BLT1 and BLT2, in mediating chemotactic signaling in leukocytes and contrast them to other structurally related leukotrienes that bind to distinct GPCRs. Finally, we highlight the specific roles of the LTB₄-BLT1 axis in mediating signal-relay between chemotaxing neutrophils and its potential contribution to a wide variety of inflammatory conditions including tumor progression and metastasis, where LTB₄ is emerging as a key signaling component.

Keywords: Chemotaxis; Inflammation; Leukotriene B(4); Migration; Neutrophils.

Figure 1.. LTB₄ synthesis and transport.

A schematic depiction of the various steps that lead to the synthesis of LTB₄, it’s packaging into MVBs and secretion as exosomes from neutrophils chemotaxing towards a primary chemoattractant.

Figure 2.. BLT1-mediated signaling in leukocyte.

A schematic representation of the signaling events that occur upon the activation of BLT1 by LTB₄. Clathrin-mediated endocytosis of BLT1, front and back signaling as well as inside-out integrin activation in a polarized neutrophil are shown.

Figure 3.. Functional roles of the LTB₄-BLT1 axis in diverse cell migration scenarios.

A pie chart depicting the diverse roles of the LTB₄-BLT1 axis in distinct situations that involve increased complexities, factors and cell-types.