Thrombospondin-1 Contributes to Mortality in Murine Sepsis through Effects on Innate Immunity

Autor: Yijie Wang, Christopher P. Baran, Anasuya Sarkar, Payal Mehta, Naeem A. Ali, Sara N. Fischer, Melissa G. Piper, Christie A. Newland, Matthew C. Exline, Clay B. Marsh, Shannon R. Balser, Carrie A. Schrader, Sara McMaken, Charles H. Cook, Gary Phillips
Rok vydání: 2011
Předmět:
Critical Care and Emergency Medicine
medicine.medical_treatment
lcsh:Medicine
Cell Count
Thrombospondin 1
Mice
0302 clinical medicine
immune system diseases
Peritoneal Lavage
lcsh:Science
Cecum
0303 health sciences
Multidisciplinary
virus diseases
3. Good health
Infectious Diseases
Cytokine
030220 oncology & carcinogenesis
Medicine
Cytokines
Inflammation Mediators
Peritoneum
medicine.symptom
Research Article
endocrine system
Inflammation
Punctures
Biology
Sepsis
03 medical and health sciences
Immune system
Phagocytosis
Immunity
medicine
Animals
Humans
Ligation
030304 developmental biology
Wound Healing
Innate immune system
Macrophages
lcsh:R
Transforming growth factor beta
medicine.disease
Survival Analysis
Bacterial Load
Immunity
Innate
Disease Models
Animal
Cytoprotection
Immunology
biology.protein
lcsh:Q
Zdroj: PLoS ONE, Vol 6, Iss 5, p e19654 (2011)
PLoS ONE
ISSN: 1932-6203
Popis: BACKGROUND:Thrombospondin-1 (TSP-1) is involved in many biological processes, including immune and tissue injury response, but its role in sepsis is unknown. Cell surface expression of TSP-1 on platelets is increased in sepsis and could activate the anti-inflammatory cytokine transforming growth factor beta (TGFβ1) affecting outcome. Because of these observations we sought to determine the importance of TSP-1 in sepsis. METHODOLOGY/PRINCIPAL FINDINGS:We performed studies on TSP-1 null and wild type (WT) C57BL/6J mice to determine the importance of TSP-1 in sepsis. We utilized the cecal ligation puncture (CLP) and intraperitoneal E. coli injection (i.p. E. coli) models of peritoneal sepsis. Additionally, bone-marrow-derived macrophages (BMMs) were used to determine phagocytic activity. TSP-1-/- animals experienced lower mortality than WT mice after CLP. Tissue and peritoneal lavage TGFβ1 levels were unchanged between animals of each genotype. In addition, there is no difference between the levels of major innate cytokines between the two groups of animals. PLF from WT mice contained a greater bacterial load than TSP-1-/- mice after CLP. The survival advantage for TSP-1-/- animals persisted when i.p. E. coli injections were performed. TSP-1-/- BMMs had increased phagocytic capacity compared to WT. CONCLUSIONS:TSP-1 deficiency was protective in two murine models of peritoneal sepsis, independent of TGFβ1 activation. Our studies suggest TSP-1 expression is associated with decreased phagocytosis and possibly bacterial clearance, leading to increased peritoneal inflammation and mortality in WT mice. These data support the contention that TSP-1 should be more fully explored in the human condition.
Databáze: OpenAIRE
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