LPS induces pulmonary intravascular macrophages producing inflammatory mediators via activating NF‐κB

Abstract

Pulmonary intravascular macrophages (PIMs) are often responsible for the clearance of blood-borne pathogens, including endotoxin, lipopolysaccharide of Gram-negative bacteria. It is well accepted that PIMs play a pivotal role in the pathogenesis of endotoxin-induced acute lung injury. However, the mechanisms by which PIMs are involved in the lipopolysaccharide-induced inflammatory responses remain unclear. Through the present study the following results were found: (1) When challenged with lipopolysaccharide (10 micrograms/ml), PIMs underwent marked cellular enlargement, intercellular adhesion plaques became longer, and some particulates were enwrapped in the pseudopods. (2) Lipopolysaccharide could up-regulate the expression of some inflammatory mediators in PIMs, including TNF-alpha, IL-1beta, IL-6, IL-8, and COX-2, and these up-regulated expression of inflammatory mediators correlated with NF-kappaB activation. (3) Dexamethasone as well as acetylsalicylic acid reduced the expression of TNF-alpha in lipopolysaccharide-challenged PIMs, and the decreased expression of TNF-alpha was also consistent with decreased NF-kappaB activation. Our results suggest that NF-kappaB activation in PIMs followed by phagocytizing lipopolysaccharide resulted in the up-regulation of TNF-alpha, IL-1beta, IL-6, IL-8, and COX-2, which could be alleviated by dexamethasone.

Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent

“…We observed that the volume of ethanol can be substantially reduced to 0.8 mL (compared with 40 mL, as published previously [22,23]), which caused moderate-to-severe TNBS-mediated inflammation with minimal discomfort to the animals. Another detail worth noting is the need to premedicate pigs with aspirin, indomethacin, or a specific thromboxane receptor blocker before injecting lipid-based particles such as MBs (16)(17)(18), because pigs have abundant intrapulmonary macrophages (26,27). These macrophages rapidly clear intravenously injected particles and immediately release substances such as vasoconstrictor thromboxane A2, with subsequent pulmonary arterial hypertension, systemic…”

“…One hour before US scanning, 2 L of a highly diluted barium sulfate suspension (VoLumen; E-Z-Em, Lake Success, NY) was administered through a nasogastric tube placed into the stomach to improve small bowel distention and to minimize intraluminal air, according to standard protocols for clinical cross-sectional small-bowel imaging (13)(14)(15). Pigs were premedicated with acetylsalicylic acid (Aspirin; Wedgewood, Swedesboro, NJ) administered either orally (3.5 mg per kilogram of body weight, every 12 hours beginning 24 hours prior to US; n = 12) or intravenously (3.5 mg/kg; 5 minutes prior to intravenous contrast agent injection; n = 11) as previously described (16)(17)(18)(19). In all pigs, imaging was performed by an abdominal radiologist (J.K.W., with 14 years of experience) using a clinical US scanner (Acuson Sequoia 512; Siemens Healthcare, Malvern, Pa) and a 15L8W clinical transducer 48 hours after the induction of ileitis.…”

Sevoflurane pretreatment prevents lipopolysaccharide (LPS)-induced acute lung injury in rats through up-regulated heme oxygenase-1 (HO-1) expression

“…LPS endotoxin, as a main component of the cell wall of gram-negative bacteria, is the most commonly used injury agent to induce ALI model (Davidson et al, 2002;Chen et al, 2003;Jeyaseelan and Chu, 2004). Therefore, in this work, the ALI model was established by intravenous injection with 5 mg/kg LPS to rats.…”

Pulmonary intravascular macrophages and lung health: What are we missing?

“…The globular surface coat of PIMs, probably anchored via a glycosyl-phosphatidyl inositol anchor, complexes with blood-borne materials such as tracer particles and endotoxins and mediates their endocytosis (3,43,46). PIM colonization of the lung occurs either early after birth in some species (constitutive PIMs) (28,65), later upon stimulation with lipopolysaccharide (LPS) and bacteria, or in conditions such as cirrhosis (induced PIMs) (11,13,45). Of the animals tested, the orders Artiodactyla (pigs, sheep, goats, llamas, reindeer, water buffalo) and Perissodactyla (horse; Fig.…”