Rubel Carolina, Fernández Gabriela C, Rosa Fernanda Alves, Gómez Sonia, Bompadre Macarena Beigier, Coso Omar A, Isturiz Martín A, Palermo Marina S
División Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
J Immunol. 2002 Apr 1;168(7):3527-35. doi: 10.4049/jimmunol.168.7.3527.
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.
整合素家族不仅介导多形核白细胞（PMN）募集至炎症部位，还通过与特定配体结合来调节多种效应功能。我们最近证明，可溶性纤维蛋白原（sFbg）能够通过整合素依赖性机制在PMN中触发激活信号。这种激活导致脱颗粒、吞噬作用增强和细胞凋亡延迟。本研究的目的是进一步阐明sFbg与人PMN中CD11b相互作用后发生的分子事件，以及该信号通路在中性粒细胞功能调节中的作用。我们证明，sFbg触发一系列细胞内信号，导致粘着斑激酶和细胞外信号调节激酶1/2酪氨酸磷酸化。这种丝裂原活化蛋白激酶途径的激活在sFbg对次级颗粒脱颗粒、抗体依赖性吞噬作用和细胞凋亡的调节中起核心作用。然而，纤维蛋白原诱导的分泌小泡脱颗粒独立于本文研究的信号转导途径发生。在炎症过程中，sFbg激活的细胞内信号通路可能是影响PMN功能的早期事件。
