Selective Depletion of Alveolar Macrophages in Polymicrobial Sepsis Increases Lung Injury, Bacterial Load and Mortality but Does Not Affect Cytokine Release

Traeger, Tobias; Keßler, Wolfram; Hilpert, A.; Mikulcak, Marlene; Entleutner, Markus; Koerner, Pia; Westerholt, Alexandra; Cziupka, Katharina; Rooijen, Nico van; Heidecke, Claus–Dieter; Maier, Stefan A.

doi:10.1159/000160953

Cited by 17 publications

(18 citation statements)

References 83 publications

(61 reference statements)

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“…CASP can be applied for all questions around sepsis or peritonitis and is therefore useful for all disciplines dealing with sepsis research, for example immunology, pharmacology, surgery, intensive care medicine, etc. A selection of publications concerning different subjects of sepsis using the CASP model is given below (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Discussionmentioning

confidence: 99%

Colon Ascendens Stent Peritonitis (CASP) - a Standardized Model for Polymicrobial Abdominal Sepsis

Traeger

Koerner

Keßler

et al. 2010

JoVE

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Sepsis remains a persistent problem on intensive care units all over the world. Understanding the complex mechanisms of sepsis is the precondition for establishing new therapeutic approaches in this field. Therefore, animal models are required that are able to closely mimic the human disease and also sufficiently deal with scientific questions. The Colon Ascendens Stent Peritonitis (CASP) is a highly standardized model for polymicrobial abdominal sepsis in rodents. In this model, a small stent is surgically inserted into the ascending colon of mice or rats leading to a continuous leakage of intestinal bacteria into the peritoneal cavity. The procedure results in peritonitis, systemic bacteraemia, organ infection by gut bacteria, and systemic but also local release of several pro-and anti-inflammatory cytokines. The lethality of CASP can be controlled by the diameter of the inserted stent. A variant of this model, the so-called CASP with intervention (CASPI), raises opportunity to remove the septic focus by a second operation according to common procedures in clinical practice. CASP is an easily learnable and highly reproducible model that closely mimics the clinical course of abdominal sepsis. It leads way to study on questions in several scientific fields e.g. immunology, infectiology, or surgery. Video LinkThe video component of this article can be found at http://www.jove.com/video/2299/ Protocol 1. Preparation of the Mouse 1. Anesthetize the mouse by intraperitoneal injection of the narcotic fluid (see table of reagents) and place it in supine position. 2. The feet of the mouse need to be fixed with tape on the plate to ensure a stable position of the animal during the operation. Operation

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Section: Discussionmentioning

confidence: 99%

Colon Ascendens Stent Peritonitis (CASP) - a Standardized Model for Polymicrobial Abdominal Sepsis

Traeger

Koerner

Keßler

et al. 2010

JoVE

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“…Though various factors lead to the occurrence of ALI [19,20,21], severe trauma is still a major cause of ALI. In a study by Treggiari et al [22], the incidence of ALI was 4–12% in 1,296 patients who survived 24 h or more after trauma.…”

Section: Discussionmentioning

confidence: 99%

Gap Junction Channel Modulates Pulmonary Vascular Permeability through Calcium in Acute Lung Injury: An Experimental Study

Zhang

Wen²,

Sun³

et al. 2010

Respiration

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Background: Increased pulmonary vascular permeability is a hallmark of acute lung injury (ALI). Gap junction channels (GJCs) connect adjacent cells and facilitate ion exchange. It remained unclear whether GJCs modulate pulmonary permeability in ALI through intracellular calcium. Objectives: This study aimed to verify if GJCs in pulmonary microvessel endothelial cells (PMVECs) modulate pulmonary vascular permeability in ALI via intracellular calcium. Methods: Firstly, an animal model of ALI was studied using connexin 40 (Cx40) inmunohistochemistry in the lung with Evans’ blue (EB) leakage. Then cultured PMVECs were divided into three groups: G_control, G_serum and G_blocker. Serum was obtained from animals with ALI following gunshot injury (injured serum). Initially, G_blocker was treated with the blocker of GJCs, and then G_serum and G_blocker were stimulated with the injured serum, respectively. GJCs, the permeability of cell monolayers and intracellular Ca²⁺ were assessed. Results: Cx40 time-dependently decreased, whereas EB leakage increased. Cx40 and EB leakage exhibited a strong inverse correlation (ρ = –0.934, p < 0.05). Injured serum decreased GJCs and expression of Cx40, whereas the blocker aggravated this effect. Similarly, when PMVEC monolayer was treated with injured serum, both permeability and intracellular Ca²⁺ increased. These effects were also aggravated with the blocker. Conclusions: Depression of GJCs of PMVECs increased pulmonary vascular permeability in ALI; this effect may be mediated by the overload of intracellular calcium.

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“…It should be noted that as well as a pattern recognition receptor, AIM is also a survival factor for macrophages, key contributors to inflammation. 18,[36][37][38][39] Future experiments need to assess which of the dual functions of AIM predominates in the early immune response against pathogens.…”

Section: Discussionmentioning

confidence: 99%

The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression

et al. 2014

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Apoptosis inhibitor of macrophages (AIMs), a homologue of human Spa, is a mouse soluble member of the scavenger receptor cysteine-rich superfamily (SRCR-SF). This family integrates a group of proteins expressed by innate and adaptive immune cells for which no unifying function has yet been described. Pleiotropic functions have been ascribed to AIM, from viability support in lymphocytes during thymic selection to lipid metabolism and anti-inflammatory effects in autoimmune pathologies. In the present report, the pathogen binding properties of AIM have been explored. By using a recombinant form of AIM (rAIM) expressed in mammalian cells, it is shown that this protein is able to bind and aggregate Gram-positive and Gram-negative bacteria, as well as pathogenic and saprophytic fungal species. Importantly, endogenous AIM from mouse serum also binds to microorganisms and secretion of AIM was rapidly induced in mouse spleen macrophages following exposure to conserved microbial cell wall components. Cytokine release induced by well-known bacterial and fungal Toll-like receptor (TLR) ligands on mouse splenocytes was also inhibited in the presence of rAIM. Furthermore, mouse models of pathogen-associated molecular patterns (PAMPs)-induced septic shock of bacterial and fungal origin showed that serum AIM levels changed in a time-dependent manner. Altogether, these data suggest that AIM plays a general homeostatic role by supporting innate humoral defense during pathogen aggression.

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Selective Depletion of Alveolar Macrophages in Polymicrobial Sepsis Increases Lung Injury, Bacterial Load and Mortality but Does Not Affect Cytokine Release

Cited by 17 publications

References 83 publications

Colon Ascendens Stent Peritonitis (CASP) - a Standardized Model for Polymicrobial Abdominal Sepsis

Colon Ascendens Stent Peritonitis (CASP) - a Standardized Model for Polymicrobial Abdominal Sepsis

Gap Junction Channel Modulates Pulmonary Vascular Permeability through Calcium in Acute Lung Injury: An Experimental Study

The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression

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