Siva Kumar SolletiSorachai SrisumaSoumyaroop BhattacharyaJavier Rangel-MorenoKaiser M. BijliTroy D. RandallArshad RahmanThomas J. MarianiUniversity of Rochester Medical CenterMahidol UniversityAtlanta VA Medical CenterUniversity of Alabama at Birmingham2018-12-112019-03-142018-12-112019-03-142016-07-01FASEB Journal. Vol.30, No.7 (2016), 2615-262615306860089266382-s2.0-84978035745https://repository.li.mahidol.ac.th/handle/20.500.14594/42985© FASEB. 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1096/fj.201500159R