Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion

Area of Science:

• Immunology
• Cell Biology

Background:

• Myeloid-related proteins (MRPs) 8 and 14 are secreted by myeloid cells as proinflammatory mediators.
• The precise function of extracellular MRP8/14 in circulating blood remains largely unknown.

Purpose of the Study:

• To elucidate the functional role of extracellular MRP8/14 in the leukocyte adhesion cascade.
• To identify the molecular mechanisms by which MRP8/14 influences leukocyte recruitment.

Main Methods:

• Investigated neutrophil rolling and adhesion under flow conditions.
• Analyzed the role of E-selectin-PSGL-1 interactions in MRP8/14 secretion.
• Examined the involvement of Toll-like receptor 4 (TLR4) and Rap1-GTPase signaling in MRP8/14-mediated effects.

Main Results:

• Extracellular MRP8/14 was identified as an autocrine factor in leukocyte adhesion.
• Neutrophil rolling, mediated by E-selectin-PSGL-1, triggers MRP8/14 secretion.
• Released MRP8/14 activates a TLR4- and Rap1-GTPase-dependent pathway, leading to rapid β2 integrin activation in neutrophils.
• This process reduces leukocyte rolling velocity and promotes adhesion.

Conclusions:

• Extracellular MRP8/14 acts as a crucial autocrine mediator in the leukocyte adhesion cascade.
• The MRP8/14-TLR4-Rap1-GTPase axis represents a novel pathway regulating neutrophil recruitment during inflammation.
• MRP8/14 and TLR4 are identified as key modulators of leukocyte recruitment in vivo.