The reason and mechanism of propylene glycol alginate sodium sulfate (PSS) mediated allergic side effect

Propylene glycol alginate sodium sulfate (PSS) is a heparinoid polysaccharide drug used in clinic for >30 years in China. But its allergy events happened from time to time and should not be ignored. Here, ammonium salt in PSS (PSS-NH₄⁺), PSS fractions with high Mw (PSS-H-Mw) and low mannuronic acid (M) to guluronic acid (G) ratio (PSS-L-M/G) were found to induce allergic response by the structure-activity and impurity-activity relationships in vitro. Furthermore, we confirmed the reason and elucidated the mechanism accounted for allergic side effect of PSS in vivo. It was found that high IgE levels in PSS-NH₄⁺ and PSS-H-Mw groups upregulate the cascade expression of Lyn-Syk-Akt or Erk and second messenger Ca²⁺, which accelerated mast cells (MCs) degranulation to release histamine, LTB4, TPS, and finally induced lung tissue injury. PSS-L-M/G caused a mild allergic symptom because it only enhanced the expression of p-Lyn and histamine release. In brief, PSS-NH₄⁺ and PSS-H-Mw were main reasons to result in allergic response. Our results suggested that it is very necessary to control the range of Mw and the content of impurities (< 1 % ammonium salt) of PSS to guarantee its safety and effectiveness in clinical treatment.