Regulation of ICAM-1 in human neutrophils.

Intercellular cell adhesion molecule 1 (ICAM-1) is a cell surface glycoprotein with a vital role in the immune response to pathogens. The expression pattern of ICAM-1 is wide-ranging, encompassing endothelial cells, epithelial cells and neutrophils. Recent work has characterized the role of ICAM-1 in murine neutrophils, but the function of human neutrophil ICAM-1 is incompletely understood. Herein, we investigated the expression and role of ICAMs in human neutrophils in vitro and in vivo. Our findings show clear expression of ICAM-1, -3 and -4 on peripheral blood-derived neutrophils and demonstrate that the pathogen-associated molecular pattern (PAMP) lipoteichoic acid (LTA) is an inducer of ICAM-1 expression in vitro. In vivo, neutrophils obtained from the pleural cavity of patients with a parapneumonic effusion display enhanced expression of ICAM-1 compared to peripheral blood- and oral cavity-derived neutrophils. Moreover, migration of peripheral blood-derived neutrophils across endothelial cells can upregulate neutrophil ICAM-1 expression. These findings indicate that PAMPs and/or cytokines, alongside transmigration, enhance neutrophil ICAM-1 expression at sites of inflammation. Mechanistically we observed that ICAM-1high neutrophils display elevated S. aureus phagocytic capacity. However, unlike murine neutrophils, ICAM-1 intracellular signaling in human neutrophils was not essential for phagocytosis of S. aureus and reactive oxygen species (ROS) generation. Taken together, these results have important implications for the regulation of neutrophil-mediated pathogen clearance.

Patients with cancer and sepsis trials: an unfair representation?

Approximately 20% of sepsis cases are thought to occur in patients with cancer. Thus, such patients are an important cohort to be represented and characterised among sepsis trials. However, patients with cancer are commonly excluded from sepsis trials, although the extent to which is unknown. In this opinion article, we discuss our findings that suggest that patients with cancer are being under-represented in sepsis trials, often with an unclear rationale. We question the validity of generalising results from sepsis trials to heterogenous cancer populations and call for wider inclusion of patients with cancer to bridge this knowledge gap in sepsis management.

Argatroban to achieve therapeutic anticoagulation in two patients with acute thrombosis and heparin resistance.

: We present two cases where argatroban was successfully used in patients with acute thrombosis requiring anticoagulant treatment where heparin resistance with unfractionated heparin had been encountered. The first case was a woman with abdominal arterial thrombosis, of unknown cause, treated with therapeutic low molecular weight heparin that developed pulmonary embolism despite therapeutic anticoagulation (and had evidence of heparin resistance on anti-Xa monitoring). The second patient had provoked abdominal arterial thrombosis from sepsis and could not attain therapeutic anticoagulation with intravenous unfractionated heparin. In both cases therapeutic anticoagulation was achieved with the use of argatroban, as a temporizing measure to treat the acute thrombotic event. Conventionally, argatroban has been described for use in heparin-induced thrombocytopenia. The use of argatroban is briefly discussed, especially in the context of heparin resistance where anticoagulation can be challenging. Further research using argatroban in heparin resistant patients could be justified.