Impact of STAB-1 level during the neutropenic state in septic patients with haematological malignancies

Abstract

Sepsis is a complex clinical syndrome characterized by systemic inflammation, vascular leakeage and organ failure representing a major therapeutic burden. Vascular leakage is an important mechanism in pathogensis and progression of sepsis process which occure due to disruption of the vascular barrier by inflammatory stimuli. Maintenance of vascular integrity is supported by the efficient removal of apoptotic endothelial cells. The phagocytic clearance of damaged cells by macrophages, a process termed efferocytosis, induces resolution of inflammation and suppression of pro-inflammatory cytokines. Macrophage Stabilin-1 (STAB-1) which is a phagocytic receptor mediating efferocytosis protects against disruption of vascular integrity in the course of sepsis and promotes clearance of apoptotic vascular endothelial cells damaged by severe inflammation. It was found that genetic deletion of STAB-1 decreased the survival of septic mice in the model of cecal ligation and puncture. Decreased sepsis survival in STAB-1 deficiency was associated with diminished efferocytosis, increased vascular permeability and enhanced organ dysfunction. It was demonstrated that STAB-1 on monocytes suppresses the activation of Th1 lymphocytes; thus, STAB-1 may also exert an immunosuppressive action. In addition, STAB-1 regulates lymphocyte migration and inflammatory cell recruitment. The aim of the present study is to measure serum levels of stablin 1 in adult patients with hematological malignancies during the neutropenic state who had any form of clinical or laboratory diagnosis of sepsis, And to correlate its level with other diagnostic and prognostic parameters.