Dataset Information

High molecular weight sodium hyaluronate improves survival of syndecan-1-deficient septic mice by inhibiting neutrophil migration.

ABSTRACT:

Methods

Sepsis was induced by cotton smoke inhalation followed by intranasal administration of Pseudomonas aeruginosa in female (> 6 months) Balb/c and syndecan-1 knockout mice. Survival of mice, lung capillary endothelial glycocalyx integrity, lung water content, and vascular hyper-permeability were determined with or without HMW-SH treatment in these mice. Effects of HMW-SH on endothelial permeability and neutrophil migration were tested in in vitro setting.

Results

In septic wildtype mice, we found a severely damaged pulmonary microvascular endothelial glycocalyx and elevated levels of shed syndecan-1 in the circulation. These changes were associated with significantly increased pulmonary vascular permeability. In septic syndecan-1 knockout mice, extravascular lung water content was higher, and early death was observed. The administration of HMW-SH significantly reduced mortality and lung water content in septic syndecan-1 knockout mice, but not in septic wildtype mice. In in vitro setting, HMW-SH inhibited neutrophil migration and reduced cultured endothelial cell permeability increases. However, these effects were reversed by the addition of recombinant syndecan-1 ectodomain.

Conclusions

HMW-SH reduced lung tissue damage and mortality in the absence of syndecan-1 protein, possibly by reducing vascular hyper-permeability and neutrophil migration. Our results further suggest that increased shed syndecan-1 protein levels are linked with the inefficiency of HMW-SH in septic wildtype mice.

SUBMITTER: Baljinnyam T

PROVIDER: S-EPMC8087021 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Heparan sulfate proteoglycans (HSPGs) are at the forefront of host-microbe interactions. Molecular and cell-based studies suggest that HSPG-pathogen interactions promote pathogenesis by facilitating microbial attachment and invasion of host cells. However, the specific identity of HSPGs, precise mechanisms by which HSPGs promote pathogenesis, and the in vivo relevance of HSPG-pathogen interactions remain to be determined. HSPGs also modulate host responses to tissue injury and inflammation, but functions of HSPGs other than facilitating microbial attachment and internalization are understudied in infectious disease. Here we examined the role of syndecan-1 (Sdc1), a major cell surface HSPG of epithelial cells, in mouse models of Listeria monocytogenes (Lm) infection. We show that Sdc1-/- mice are significantly less susceptible to both intragastric and intravenous Lm infection compared to wild type (Wt) mice. This phenotype is not seen in Sdc3-/- or Sdc4-/- mice, indicating that ablation of Sdc1 causes a specific gain of function that enables mice to resist listeriosis. However, Sdc1 does not support Lm attachment or invasion of host cells, indicating that Sdc1 does not promote pathogenesis as a cell surface Lm receptor. Instead, Sdc1 inhibits the clearance of Lm before the bacterium gains access to its intracellular niche. Large intravascular aggregates of neutrophils and neutrophil extracellular traps (NETs) embedded with antimicrobial compounds are formed in Sdc1-/- livers, which trap and kill Lm. Lm infection induces Sdc1 shedding from the surface of hepatocytes in Wt livers, which is directly associated with the decrease in size of intravascular aggregated NETs. Furthermore, administration of purified Sdc1 ectodomains or DNase inhibits the formation of intravascular aggregated neutrophils and NETs and significantly increases the liver bacterial burden in Sdc1-/- mice. These data indicate that Lm induces Sdc1 shedding to subvert the activity of Sdc1 ectodomains to inhibit its clearance by intravascular aggregated NETs.

Project description:Background:Recent artificial tear preparations have provided 0.2% concentration of sodium hyaluronate. However, no published data exist on their potential superiority against 0.1% in alleviating dry-eye-disease symptoms in cataract extraction surgery. Methods:A total of 180 patients that underwent cataract extraction surgery were randomly divided into 2 groups according to their postoperative regime: Study group (SG) received fixed combination of tobramycin and dexamethasone (FCTD) quid for 3?weeks, and additionally 0.2% sodium hyaluronate provided in the COMOD® device quid for 6?weeks. Control group (CG) received fixed combination of tobramycin and dexamethasone (FCTD) quid for 3?weeks, and additionally 0.1% sodium hyaluronate provided in the COMOD® device quid for 6?weeks. The following indexes were evaluated at 3 postoperative checkpoints: 1) Surface discomfort index (SDI) which was derived by four direct 10-scale Likert-type questions that were addressed to the patient and pertained to: a) foreign body sensation (FBS), b) blinking discomfort (BD), c) stinging sensation (SS), d) tearing sensation (TS), 2) Tear break-up time (TBUT), 3) Schirmer's test, 4) Central corneal thickness (CCT), and 4) Central Corneal Sensitivity (CCS). Results:Both groups showed reduced CCS values at all postoperative examination points; however, SG participants had significantly better CCS (all p <?0.05). SG had better TBUT than CG at the 3rd (p =?0.03) and 6th examination points (p =?0.04). Moreover, SG had better SDI scores at the 3rd (SDI?=?9.26?±?0.55) and 6th weeks (SDI?=?9.47?±?0.48) vs. CG participants (p =?0.03 and p <?0.01, respectively). Conclusion:The increased 0.2% sodium hyaluronate concentration in the artificial tears provided in the COMOD® device seems to address dry-eye-disease symptoms better in patients who underwent phacoemulsification surgery than the 0.1% concentration. Trial registration:ClinicalTrials.gov Identifier: NCT03705949 Oct 15, 2018, retrospectively registered.