High and Low Molecular Weight Hyaluronic Acid Differentially Influence Macrophage Activation

TLDR

Macrophages display phenotypic diversity, and hyaluronic acid signals differently depending on its molecular weight. The study aimed to determine how hyaluronic acid molecular weight influences macrophage activation and reprogramming. Activation markers were quantified by qRT‑PCR and cytokine ELISAs in macrophages treated with low‑ or high‑molecular‑weight hyaluronic acid under resting, classically activated, and post‑inflammatory conditions. Low‑molecular‑weight hyaluronic acid induced a classically activated‑like state in macrophages, evidenced by up‑regulation of pro‑inflammatory genes.

Abstract

Macrophages exhibit phenotypic diversity permitting wide-ranging roles in maintaining physiologic homeostasis. Hyaluronic acid, a major glycosaminoglycan of the extracellular matrix, has been shown to have differential signaling based on its molecular weight. With this in mind, the main objective of this study was to elucidate the role of hyaluronic acid molecular weight on macrophage activation and reprogramming. Changes in macrophage activation were assessed by activation state selective marker measurement, specifically quantitative real time polymerase chain reaction, and cytokine enzyme-linked immunoassays, after macrophage treatment with differing molecular weights of hyaluronic acid under four conditions: the resting state, concurrent with classical activation, and following inflammation involving either classically or alternatively activated macrophages. Regardless of initial polarization state, low molecular weight hyaluronic acid induced a classically activated-like state, confirmed by up-regulation of pro-inflammatory genes, including