Effects of Inhaled Low Molecular Weight Heparin on Airway Allergic Inflammation in Aerosol-Ovalbumin-Sensitized Guinea Pigs

Abstract

Low molecular weigh, heparin (LMWH) possesses multiple nonanticoagulant properties. In the present study, we observed its anti-airway allergic inflammatory effects by bronchoalveolar lavage in guinea pigs. Guinea pigs were sensitized by repeatedly inhaling aerosolized ovalbumin. LMWH (400 u/l, 800 u/l), dexamethasone (1.2 mg/1) or vehicle (normal saline) was inhaled for 7 days. Then the animals were sacrificed under anesthesia and then lavaged with ice-cold Hank's buffer immediately; bronchoalveolar lavage fluid (BALF) was prepared 24 h after the animals were challenged by antigen exposure. The effects of LMWH on total cell counts, absolute eosinophil counts and cell catalogues in BALF were studied; effects on the activity of eosinophil peroxidase (EPO) and the contents of histamine and eosinophil cationic protein (ECP) in BALF supernatant were detected. Our results showed that compared with the vehicle group, LMWH at 400 u/l and 800 u/1 could significantly reduce total cell counts, absolute eosinophil counts and percentage of eosinophils in BALF (P<0.05 and P<0.01, respectively); LMWH at 800 u/l markedly inhibited the activity of EPO in BALF supernatant (P<0.05); LMWH at 400 u/l and 800 u/l remarkably reduced the content of histamine in BALF supernatant (P<0.05 and P<0.01, respectively), LMWH at 800 u/l decreased the content of ECP (P<0.05) significantly. It suggested that LMWH exerted anti-airway allergic inflammatory action by inhibiting infiltration of inflammatory cells and reducing release of inflammatory mediators, as well as antagonizing their activities, and that LMWH could be developed as a potential anti-bronchial asthmatic drug.

Heparan sulfate proteoglycans in extravasation: assisting leukocyte guidance

“…Setting HS (PGs) as therapeutics Heparin, low molecular weight heparin Cerebral ischemia (38), peritonitis (39,155,172), delayed type hypersensitivity (39), meningitis (173), allergic encephalomyelitis (174), airway (allergic) inflammation (175)(176)(177)(178)(179), hepatic ischemia/reperfusion (180), cutaneous inflammation (178,181), myocarditis (182), renal ischemia/reperfusion (183,184) marrow, via presentation of the stem cell chemokine stromal derived factor-1 and adhesive interaction with Lselectin (48,91,148). Interestingly, bone marrow endothelial cells were shown to express more highly sulfated HS than human umbilical vein endothelial cells, favoring both chemokine and L-selectin binding (149).…”

The quest for non-invasive delivery of bioactive macromolecules: A focus on heparins

“…This issue has received considerable attention, and resulted in the design and development of varied devices to provide consistent drug delivery to the deep lung tissue [116]. The effective and safe delivery of heparins by this route may be clinically relevant not only for the systemic effect against thrombosis but also for the improvement of localized pharmacotherapy such as in cases of allergy and asthma management [117][118][119].…”

The potential of low molecular weight heparin to mitigate cytokine storm in severe COVID-19 patients: a retrospective clinical study

“…Substantial studies have reported that low molecular weight heparin (LMWH) has various non-anticoagulant properties 12 that play an anti-inflammatory role by reducing the release of IL-6. 13-15 However, the anti-inflammatory effects of LMWH in COVID-19 are currently unknown.…”