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A4756 - Protein Phospholipid Transfer ProteinandAlpha-1 Antitrypsin Regulate Neutrophil Immune Responses
Author Block: S. Nath1, P. O. Ochieng2, R. Macarulay3, A. Dabo1, E. Eden2, M. A. Campos4, X. Jiang1, R. F. Foronjy1, P. Geraghty1; 1SUNY Downstate Medical Center, Brooklyn, NY, United States, 2St Lukes-Roosevelt Hosp Ctr, New York, NY, United States, 3Trinity college, Dublin, Ireland, 4Medicine/Pulmonary, Univ of Miami, Miami, FL, United States.
Introduction/rationale: Excessive neutrophil degranulation is a common feature of many inflammatory disorders, including alpha-1 antitrypsin (AAT) deficiency. Phospholipid transfer protein (PLTP) prevents neutrophil degranulation but serine proteases cleave PLTP in the airways. We propose that PLTP can prevent degranulation of neutrophils isolated from AAT deficient subjects, and PLTP deficiency enhances neutrophil degranulation responses in mice.Methods used: Neutrophils were isolated from venous peripheral blood of PiMM and PiZZ AAT genotype subjects (n=14/group). Neutrophils were exposed to PLTP prior to stimulation with leukotriene B4 (LTB4) and neutrophil degranulation was recorded. Degranulation was also examined in neutrophils isolated from Pltp knockout mice and wild type control mice.Results of the study: Stimulation with LTB4 induced degranulation of primary, secondary and tertiary granules in neutrophils isolated from both AAT genotypes. However, neutrophils from PiZZ subjects had heighted degranulation responses. PLTP treatment reduced degranulation responses in neutrophils from both groups. Loss of Pltp expression resulted in enhanced degranulation in neutrophils from mice compared to wild type mice.Conclusions of the study: PLTP mediates neutrophil responses and loss of PLTP function, via enhanced serine protease responses and reduced AAT, could contribute to elevated neutrophil associated signaling in the lung.