Dr. Karina Serban

Alpha 1 antitrypsin treatment increases mannose binding lectin anti-inflammatory function in lung macrophages

The innate immune response is crucial in chronic inflammatory airway diseases, like COPD, AATD, or cystic fibrosis. The airways of these patients are characterized by colonization with Gram-negatives bacteria and concomitant high percentage of apoptotic cells, resulting in abnormal clearance of pathogens, persistent inflammation, and recurrent infectious exacerbations. Mannose binding lectin (MBL) and its binding partner MBL-associated serine protease (MASP) are collectins involved in complement-mediated bacterial phagocytosis and pro-inflammatory alveolar macrophage (AM) / peripheral blood monocyte cells (PBMC) response. Alternatively, MBL binds the AM mannose receptor and enhances efferocytosis of apoptotic cells by the anti-inflammatory AM / PBMC. Decreased MBL levels in individuals with recurrent airway infections suggest an important role in pulmonary defense; however the effects of A1AT deficiency and replacement therapy on MBL pathway are currently not understood.

Aim:

Dr. Serban hypothesizes that AATD is associated with decreased plasma and bronchoalveolar fluid MBL levels and pro-inflammatory AM and PBMC gene expression, while A1AT therapy increases MBL levels and AM and PBMC anti-inflammatory gene expression associated with the inhibition of MASP.

Aim 1: to compare MBL levels in PiZZ individuals off and on A1AT therapy to healthy individuals and correlate MBL levels with AM and PBMC gene expression arrays.

Aim 2: To establish that A1AT inhibits MASP, increases MBL to mannose receptor binding and AM / PBMC anti-inflammatory phenotype. 

Curriculum Vitae Dr. Karina Serban

Karina received her MD degree in the Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Her working experience brought her to the US where she was first Assistant Research Professor/ Assistant Professor of Clinical Medicine in the Department of Medicine, Division of Pulmonary, Allergy, Critical Care, Occupational and Sleep Medicine of the Indiana University, Indianapolis.

She is currently an Assistant Professor of Medicine in the Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine of the National Jewish Health, Denver, Colorado

Her project „Alpha 1 antitrypsin treatment increases mannose binding lectin (MBL) anti-inflammatory function in lung macrophages" aims to advance the current understanding of AAT biology during innate immune response and identify MBL as a biomarker and therapeutic target in the COPD and AAT-deficient lung.

Contact
Dr. Karina Serban
National Jewish Health
1400 Jackson Street, Denver
Colorado, USA