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Previous studies have shown that phagocytosis of apoptotic cells can tune the macrophage phenotype and trigger the resolution of inflammation. This mechanism is largely dependent on the recognition of phosphatidylserine (PS) residues on the outer membrane of dying cells. Therefore, we sought to assess the effects of PS-containing liposomes (mimics of apoptotic cells) on the leukocyte migration profile during the inflammatory process in vivo. Inflammation was induced by carrageenan injection into air pouches created on the dorsal region of mice, as this model enables convenient access to the exudates for further investigation. Mice were treated with PBS, PS-containing or phosphatidylcholine (PC)-containing liposomes (10, 30 or 100 mg/kg intraperitoneally [i.p.]). Starting 8 h after carrageenan injection, the level of leukocyte infiltration was monitored over three days. The PS-containing, but not PC-containing, liposomes reduced the polymorphonuclear (PMN) and mononuclear (MN) leukocyte influx into the inflamed pouches in a dose-dependent fashion. Most notably, these effects could also be adoptively transferred; that is, they were also found in mice injected with a liposome-free peritoneal lavage obtained from the mice that had received the intraperitoneal PS-liposome treatment. The effect of treatment with the PS-induced soluble mediators (PS-ISMs) was found to be dependent on the presence of peritoneal macrophages and was susceptible to heat, trypsin degradation, and cycloheximide treatment. The PS-containing liposomes promoted the reduction of PMN leukocyte influx by triggering the release of anti-inflammatory autacoids with a proteinaceous nature that were produced de novo after PS exposure., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of the present work is to provide a better comprehension of the pneumonia-induced sepsis model through temporal evaluation of several parameters, and thus identify the main factors that determine mortality in this model. Klebsiella pneumoniae was inoculated intratracheally in anesthetized Swiss male mice. Inflammatory and cardiovascular parameters were evaluated 6, 24 and 48 h after the insult. The results show that severity of infection and the mortality correlated with the amount of bacteria. Six, 24 and 48 h after inoculation, animals presented pathological changes in lungs, increase in cell number in the bronchoalveolar lavage, leukopenia, increase in TNF-α and IL-1β levels, hypotension and hyporesponsiveness to vasoconstrictors, the two latter characteristics of severe sepsis and septic shock. Significant numbers of bacteria in spleen and heart homogenates indicated infection spreading. Interestingly, NOS-2 expression appeared late after bacteria inoculation, whereas levels of NOS-1 and NOS-3 were unchanged. The high NOS-2 expression coincided with an exacerbated NO production in the infection focus and in plasma, as judging by nitrate + nitrite levels. This study shows that K. pneumoniae inoculation induces a systemic inflammatory response and cardiovascular alterations, which endures at least until 48 h. K. pneumoniae-induced lung infection is a clinically relevant animal model of sepsis and a better understanding of this model may help to increase the knowledge about sepsis pathophysiology., (© 2013 The Authors. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.)