Syndecan 1 shedding contributes to Pseudomonas aeruginosa sepsis.

Abstract

The innate immune system is comprised of many components that function coordinately to prevent bacterial sepsis. However, thermal injury suppresses many of these factors, and the opportunistic pathogen Pseudomonas aeruginosa takes advantage of this condition, making it one of the leading causes of morbidity and mortality in the setting of thermal injury. P. aeruginosa is extremely efficient at colonizing burn wounds, spreading systemically, and causing sepsis, which often results in a systemic inflammatory response, multiple-organ failure, and death. The pathogenicity of P. aeruginosa is due to the arsenal of virulence factors produced by the pathogen and the immunocompromised state of the host. Syndecan 1 is a major heparan sulfate proteoglycan present on many host cells involved in thermal injury. Syndecan 1 anchored to the cell surface can be cleaved in a process termed ectodomain shedding. Syndecan 1 shedding results in the release of intact, soluble proteoglycan ectodomains that have diverse roles in innate immunity. Here we show for the first time that thermal injury results in shedding of syndecan 1 from host tissue. Our data show that syndecan 1 null mice are significantly less susceptible to P. aeruginosa infection than their wild-type counterparts, as demonstrated by (i) significantly lower mortality; (ii) absence of systemic spread of P. aeruginosa; and (iii) significant reductions in some proinflammatory cytokines. These results suggest that shed syndecan 1 plays an important role in the pathogenesis of P. aeruginosa infection of thermal injury and that syndecan 1-neutralizing agents may be effective supplements to current P. aeruginosa treatments.

• Authors: Allan Haynes 3rd, Frank Ruda, Jeffrey Oliver, Abdul N Hamood, John A Griswold, Pyong Woo Park, Kendra P Rumbaugh
• Journal: Infection and immunity (Infect Immun) Vol. 73 Issue 12 Pg. 7914-21 (Dec 2005) ISSN: 0019-9567 [Print] United States
• PMID: 16299282 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Membrane Glycoproteins
• Proteoglycans
• Sdc1 protein, mouse
• Syndecan-1
• Syndecans

Topics

• Animals
• Blood Vessels (microbiology)
• Burns (genetics, metabolism, microbiology)
• Cytokines (metabolism)
• Disease Susceptibility
• Hot Temperature
• Membrane Glycoproteins (genetics, metabolism)
• Mice
• Mice, Knockout
• Proteoglycans (genetics, metabolism)
• Pseudomonas Infections (immunology, metabolism, microbiology)
• Pseudomonas aeruginosa
• Sepsis (immunology, metabolism, microbiology)
• Syndecan-1
• Syndecans