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Soluble fibrinogen modulates neutrophil functionality through the activation of an extracellular signal-regulated
Carolina Rubel1, Gabriela C Fernández, Fernanda Alves Rosa
1División Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina. rubel@sinectis.com.ar
Abstract:
The integrin family not only mediates the recruitment of polymorphonuclear leukocytes (PMN) to sites of inflammation but also regulates several effector functions by binding to specific ligands. We have recently demonstrated that soluble fibrinogen (sFbg) is able to trigger an activating signal in PMN through an integrin-dependent mechanism. This activation results in degranulation, phagocytosis enhancement, and apoptosis delay. The aim of the present work was to further elucidate the molecular events that follow sFbg interaction with CD11b in human PMN, and the participation of this signaling pathway in the regulation of neutrophil functionality. We demonstrate that sFbg triggers a cascade of intracellular signals that lead to focal adhesion kinase and extracellular signal-regulated kinase 1/2 tyrosine phosphorylation. The activation of this mitogen-activated protein kinase pathway plays a central role in the sFbg modulation of secondary granule degranulation, Ab-dependent phagocytosis, and apoptosis. However, fibrinogen-induced secretory vesicle degranulation occurs independently of the signaling transduction pathways investigated herein. In the context of an inflammatory process, the intracellular signal pathway activated by sFbg may be an early event influencing the functionality of PMN.
Insights
Soluble fibrinogen (sFbg) activates human neutrophils via integrin CD11b, triggering intracellular signals that regulate degranulation, phagocytosis, and apoptosis. This pathway influences neutrophil function during inflammation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- The integrin family mediates leukocyte recruitment and effector functions.
- Soluble fibrinogen (sFbg) activates polymorphonuclear leukocytes (PMN) via integrins.
- sFbg-induced PMN activation enhances degranulation, phagocytosis, and delays apoptosis.
Purpose of the Study:
- To investigate the molecular events following sFbg interaction with CD11b in human PMN.
- To determine the role of this signaling pathway in regulating neutrophil functionality.
Main Methods:
- Investigated intracellular signaling cascades triggered by sFbg in human PMN.
- Analyzed the impact of sFbg on focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK1/2) phosphorylation.
- Assessed the role of the mitogen-activated protein kinase (MAPK) pathway in sFbg-mediated neutrophil functions.
Main Results:
- sFbg triggers intracellular signals leading to FAK and ERK1/2 tyrosine phosphorylation.
- MAPK pathway activation is central to sFbg modulation of secondary granule degranulation, Ab-dependent phagocytosis, and apoptosis.
- Secretory vesicle degranulation induced by fibrinogen is independent of the investigated signaling pathways.
Conclusions:
- sFbg binding to CD11b initiates intracellular signaling, including MAPK activation, influencing key neutrophil functions.
- The identified intracellular signal pathway activated by sFbg may represent an early event in inflammatory processes, modulating PMN functionality.
- Understanding these pathways is crucial for comprehending neutrophil behavior in inflammation.