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CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock.

ABSTRACT: CD6 is a lymphocyte receptor that belongs to the scavenger receptor cysteine-rich superfamily. Because some members of the scavenger receptor cysteine-rich superfamily act as pattern recognition receptors for microbial components, we studied whether CD6 shares this function. We produced a recombinant form of the ectodomain of CD6 (rsCD6), which was indistinguishable (in apparent molecular mass, antibody reactivity, and cell binding properties) from a circulating form of CD6 affinity-purified from human serum. rsCD6 bound to and aggregated several Gram-positive and -negative bacterial strains through the recognition of lipoteichoic acid and LPS, respectively. The Kd of the LPS-rsCD6 interaction was 2.69 +/- 0.32 x 10(-8) M, which is similar to that reported for the LPS-CD14 interaction. Further experiments showed that membrane CD6 also retains the LPS-binding ability, and it results in activation of the MAPK signaling cascade. In vivo experiments demonstrated that i.p. administration of rsCD6 before lethal LPS challenge significantly improved mice survival, and this was concomitant with reduced serum levels of the proinflammatory cytokines TNF-alpha, IL6, and IL-1beta. In conclusion, our results illustrate the unprecedented bacterial binding properties of rsCD6 and support its therapeutic potential for the intervention of septic shock syndrome or other inflammatory diseases of infectious origin.

SUBMITTER: Sarrias MR

PROVIDER: S-EPMC1913855 | biostudies-other | 2007 Jul

REPOSITORIES: biostudies-other

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CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock.

Sarrias Maria-Rosa MR Farnós Montserrat M Mota Rubén R Sánchez-Barbero Fernando F Ibáñez Anna A Gimferrer Idoia I Vera Jorge J Fenutría Rafael R Casals Cristina C Yélamos José J Lozano Francisco F

Proceedings of the National Academy of Sciences of the United States of America 20070629 28

CD6 is a lymphocyte receptor that belongs to the scavenger receptor cysteine-rich superfamily. Because some members of the scavenger receptor cysteine-rich superfamily act as pattern recognition receptors for microbial components, we studied whether CD6 shares this function. We produced a recombinant form of the ectodomain of CD6 (rsCD6), which was indistinguishable (in apparent molecular mass, antibody reactivity, and cell binding properties) from a circulating form of CD6 affinity-purified fro ...[more]

PMID: 17601777

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Project description:Clinical guidelines recommend norepinephrine as initial vasopressor of choice for septic shock, with dopamine suggested as an alternative vasopressor in selected patients with low risk of tachyarrhythmias and absolute or relative bradycardia. We sought to determine practice patterns and outcomes associated with vasopressor selection in a large, population-based cohort of patients with septic shock that allows for assessment of outcomes in clinically important subgroups.We performed a retrospective cohort study to determine factors associated with choice of dopamine as compared with norepinephrine as initial vasopressor for patients with septic shock. We used propensity score matching to compare risk of hospital mortality based on initial vasopressor. We performed multiple sensitivity analyses using alternative methods to address confounding and hospital-level clustering. We investigated interaction between vasopressor selection and mortality in clinical subgroups based on arrhythmia and cardiovascular risk.Enhanced administrative data (Premier, Charlotte, NC) from 502 U.S. hospitals during the years 2010-2013.A total of 61,122 patients admitted with septic shock who received dopamine or norepinephrine as initial vasopressor during the first 2 days of hospitalization.None.Norepinephrine (77.6%) was the most frequently used initial vasopressor during septic shock. Dopamine was preferentially selected by cardiologists, in the Southern United States, at nonteaching hospitals, for older patients with more cardiovascular comorbidities and was used less frequently over time. Patients receiving dopamine experienced greater hospital mortality (propensity-matched cohort: n = 38,788; 25% vs 23.7%; odds ratio, 1.08; 95% CI, 1.02-1.14). Sensitivity analyses showed similar results. Subgroup analyses showed no evidence for effect modification based on arrhythmia risk or underlying cardiovascular disease.In a large population-based sample of patients with septic shock in the United States, use of dopamine as initial vasopressor was associated with increased mortality among multiple clinical subgroups. Areas where use of dopamine as initial vasopressor is more common represent potential targets for quality improvement intervention.

Dataset Information

CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock.

Publications

CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock.

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