No abstract

Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1-and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositolanchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AATdeficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

This study demonstrates that laparoscopic surgery appears to be associated with similar metabolic responses compared with open surgery, while immune parameters vary greatly between groups. The beneficial effects of laparoscopic surgery may relate, in part, to preservation of immune function in the postoperative period.

Summary Activation-induced cell death (AICD) is the process by which cells undergo apoptosis in a controlled manner through the interaction of a death factor and its receptor. Programmed cell death can be induced by a number of physiological and pathological factors including Fas (CD95)-Fas ligand (FasL/CD95L) interaction, tumour necrosis factor (TNF), ceramide, and reactive oxygen species (ROS). Fas is a 48-kDa type I transmembrane protein that belongs to the TNF/nerve growth factor receptor superfamily. FasL is a 40-kDa type II transmembrane protein that belongs to the TNF superfamily. The interaction of Fas with FasL results in a series of signal transductions which initiate apoptosis. The induction of apoptosis in this manner is termed AICD. Activation-induced cell death and Fas-FasL interactions have been shown to play significant roles in immune system homeostasis. In this review the involvement of Fas and Fas ligand in cell death, with particular reference to the T cell, and the mechanism(s) by which they induce cell death is described. The role of AICD in immune system homeostasis and the controversy surrounding the role of FasL in immune privilege, inflammation, and so-called tumour counterattack is also discussed.