School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
School of Preclinical Medicine, Chengdu University, Chengdu, Sichuan, China.
Int Immunopharmacol. 2024 Jun 15;134:112236. doi: 10.1016/j.intimp.2024.112236. Epub 2024 May 13.
Chronic rhinosinusitis (CRS) represents a heterogeneous disorder primarily characterized by the persistent inflammation of the nasal cavity and paranasal sinuses. The subtype known as chronic rhinosinusitis with nasal polyposis (CRSwNP) is distinguished by a significantly elevated recurrence rate and augmented challenges in the management of nasal polyps. The pathogenesis underlying this subtype remains incompletely understood. Macrophages play a crucial role in mediating the immune system's response to inflammatory stimuli. These cells exhibit remarkable plasticity and heterogeneity, differentiating into either the pro-inflammatory M1 phenotype or the anti-inflammatory and reparative M2 phenotype depending on the surrounding microenvironment. In CRSwNP, macrophages demonstrate reduced production of Interleukin 10 (IL-10), compromised phagocytic activity, and decreased autophagy. Dysregulation of pro-resolving mediators may occur during the inflammatory resolution process, which could potentially hinder the adequate functioning of anti-inflammatory macrophages in facilitating resolution. Collectively, these factors may contribute to the prolonged inflammation observed in CRSwNP. Additionally, macrophages may enhance fibrin cross-linking through the release of factor XIII-A (FAXIII), promoting fibrin deposition and plasma protein retention. Macrophages also modulate vascular permeability by releasing Vascular endothelial growth factor (VEGF). Moreover, they may disrupt the balance between Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs), which favors extracellular matrix (ECM) degradation, edema formation, and pseudocyst development. Accumulating evidence suggests a close association between macrophage infiltration and CRSwNP; however, the precise mechanisms underlying this relationship warrant further investigation. In different subtypes of CRSwNP, different macrophage phenotypic aggregations trigger different types of inflammatory features. Increasing evidence suggests that macrophage infiltration is closely associated with CRSwNP, but the mechanism and the relationship between macrophage typing and CRSwNP endophenotyping remain to be further explored. This review discusses the role of different types of macrophages in the pathogenesis of different types of CRSwNP and their contribution to polyp formation, in the hope that a better understanding of the role of macrophages in specific CRSwNP will contribute to a precise and individualized understanding of the disease.
慢性鼻-鼻窦炎（CRS）代表了一种异质性疾病，主要特征为鼻腔和鼻旁窦的持续性炎症。一种称为伴有鼻息肉的慢性鼻-鼻窦炎（CRSwNP）的亚型的特点是复发率显著升高，并且在管理鼻息肉方面面临更大的挑战。该亚型的发病机制仍不完全清楚。巨噬细胞在介导免疫系统对炎症刺激的反应中起着至关重要的作用。这些细胞表现出显著的可塑性和异质性，根据周围的微环境分化为促炎的 M1 表型或抗炎和修复的 M2 表型。在 CRSwNP 中，巨噬细胞表现出白细胞介素 10（IL-10）产生减少、吞噬活性受损和自噬减少。在炎症消退过程中，促解决介质的失调可能发生，这可能会妨碍抗炎巨噬细胞在促进消退方面的充分功能。这些因素可能共同导致 CRSwNP 中观察到的炎症持续存在。此外，巨噬细胞可能通过释放因子 XIII-A（FAXIII）增强纤维蛋白交联，促进纤维蛋白沉积和血浆蛋白保留。巨噬细胞还通过释放血管内皮生长因子（VEGF）来调节血管通透性。此外，它们可能破坏基质金属蛋白酶（MMPs）和组织抑制剂的金属蛋白酶（TIMPs）之间的平衡，有利于细胞外基质（ECM）降解、水肿形成和假性囊肿发展。越来越多的证据表明，巨噬细胞浸润与 CRSwNP 密切相关；然而，这种关系的确切机制需要进一步研究。在不同类型的 CRSwNP 中，不同的巨噬细胞表型聚集触发不同类型的炎症特征。越来越多的证据表明，巨噬细胞浸润与 CRSwNP 密切相关，但巨噬细胞浸润的机制以及与 CRSwNP 表型的关系仍有待进一步探索。本综述讨论了不同类型的巨噬细胞在不同类型的 CRSwNP 发病机制中的作用及其对息肉形成的贡献，希望对巨噬细胞在特定 CRSwNP 中的作用有更好的理解，有助于对疾病有更精确和个体化的认识。
