Lung Hyaluronasome: Involvement of Low Molecular Weight Ha (Lmw-Ha) in Innate Immunity

Abstract

Hyaluronic acid (HA) is a major component of the extracellular matrix. It is synthesized by hyaluronan synthases (HAS) into high-molecular-weight chains (HMW-HA) that exhibit anti-inflammatory and immunomodulatory functions. In damaged, infected, and/or inflamed tissues, HMW-HA are degraded by hyaluronidases (HYAL) or reactive oxygen species (ROS) to give rise to low-molecular-weight HAs (LMW-HAs) that are potent pro-inflammatory molecules. Therefore, the size of HA regulates the balance of anti- or pro-inflammatory functions. The activities of HA depend also on its interactions with hyaladherins. HA synthesis, degradation, and activities through HA/receptors interactions define the hyaluronasome. In this review, a short overview of the role of high and low-molecular-weight HA polymers in the lungs is provided. The involvement of LMW-HA in pulmonary innate immunity via the activation of neutrophils, macrophages, dendritic cells, and epithelial cells is described to highlight LMW-HA as a therapeutic target in inflammatory respiratory diseases. Finally, the possibilities to counter LMW-HA’s deleterious effects in the lungs are discussed.

Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection

“…TNF and interferons [52] ), including in viral respiratory infections [53] . HA is degraded in part by the activity of hyaluronidases [ 30 , 54 , 55 ] which catalyze the cleavage of HMW-HA strands into smaller, LMW-HA fragments generally of <120 kDa [ 30 , 56 ]. Mechanical force, injury, infection, and oxidative stress also contribute to HA catabolism and result in LMW-HA [ 57 , 58 ].…”

The relationship of ALPK1, hyaluronic acid and M1 macrophage polarization in the temporomandibular joint synovitis

“…HA mainly functions through CD44, TLR2 and TLR4 50 . Specifically, LMW‐HA promotes inflammation by activating the TLR2 and TLR4 signalling pathways, 51 while its binding affinity with CD44 is lower 52 . HMW‐HA inhibits inflammation by regulating the TLR2, TLR4 and CD44 signalling pathways 53,54 .…”

Anti-arthritis Effects of Zingiberaceae Extracts on Models of Inflammatory Joint Disease

“…the hyaluronan synthase 3 (HAS3) gene produces low-molecularweight HA, a potent pro-inflammatory molecule [25]. However, this study did not evaluate the size of HA released in the culture medium.…”

“…The cyclical pattern study of the INOS gene should be further investigated to determine the time point of the highest expression level. Recently, it has been reported that the hyaluronan synthase 3 ( HAS3 ) gene produces low-molecular-weight HA, a potent pro-inflammatory molecule 25 . However, this study did not evaluate the size of HA released in the culture medium.…”