title: Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation.
abstract: Serine proteinase inhibitor, clade E, member 2 (SERPINE2), is a cell- and extracellular matrix-associated inhibitor of thrombin. Although SERPINE2 is a candidate susceptibility gene for chronic obstructive pulmonary disease, the physiologic role of this protease inhibitor in lung development and homeostasis is unknown. We observed spontaneous monocytic-cell infiltration in the lungs of Serpine2-deficient (SE2(-/-)) mice, beginning at or before the time of lung maturity, which resulted in lesions that resembled bronchus-associated lymphoid tissue (BALT). The initiation of lymphocyte accumulation in the lungs of SE2(-/-) mice involved the excessive expression of chemokines, cytokines, and adhesion molecules that are essential for BALT induction, organization, and maintenance. BALT-like lesion formation in the lungs of SE2(-/-) mice was also associated with a significant increase in the activation of thrombin, a recognized target of SE2, and excess stimulation of NF-κB, a major regulator of chemokine expression and inflammation. Finally, systemic delivery of thrombin rapidly stimulated lung chemokine expression in vivo These data uncover a novel mechanism whereby loss of serine protease inhibition leads to lung lymphocyte accumulation.-Solleti, S. K., Srisuma, S., Bhattacharya, S., Rangel-Moreno, J., Bijli, K. M., Randall, T. D., Rahman, A., Mariani, T. J. Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation.
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA;
authors.forename: Siva Kumar
authors.initials: SK
authors.lastname: Solleti
authors.affiliation: Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand;
authors.forename: Sorachai
authors.initials: S
authors.lastname: Srisuma
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA;
authors.forename: Soumyaroop
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, New York, USA;
authors.forename: Javier
authors.initials: J
authors.lastname: Rangel-Moreno
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA; Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University/Atlanta Veterans Affairs Medical Center, Atlanta, Georgia, USA;
authors.forename: Kaiser M
authors.initials: KM
authors.lastname: Bijli
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, New York, USA; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Troy D
authors.initials: TD
authors.lastname: Randall
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA;
authors.forename: Arshad
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA; tom_mariani@urmc.rochester.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Mariani
mesh_terms: D000818:Animals; D001980:Bronchi / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology; D008168:Lung / Q000166:cytology*; D008214:Lymphocytes / Q000502:physiology*; D008221:Lymphoid Tissue / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D058258:Serpin E2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D058258:Serpin E2; C511869:Serpine2 protein, mouse
keywords: chemokines; protease nexin-1; serine protease inhibitor; tertiary lymphoid structures; thrombin