Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Basic Science Investigations Respiration 2012;83:61–73 DOI: 10.1159/000329868 Pulmonary Haptoglobin and CD163 Are Functional Immunoregulatory Elements in the Human Lung M. Abdullah   a D. Kähler   a C. Vock   b N. Reiling   c C. Kugler   e D. Drömann   f J. Rupp   g H.P. Hauber   d H. Fehrenbach   b P. Zabel   d, f E. Vollmer   a K. Dalhoff   f T. Goldmann   a   a  Clinical and Experimental Pathology, b  Experimental Pneumology, Inflammation and Regeneration, and Departments of c  Molecular Infection Biology and d  Clinical Medicine, Research Center Borstel, Borstel, e  Department of Thoracic Surgery, Hospital Grosshansdorf, Grosshansdorf, f  Medical University Hospital III, University Lübeck, and g  Medical Clinic III, Campus Lübeck/Institute of Medical Microbiology and Hygiene, University of Schleswig-Holstein, Lübeck, Germany bridization, immunofluorescence, real-time PCR, RT-PCR, slot and Western immunoblot analyses with tissue lysates and culture supernatants as well as ELISA and cytometric bead array analyses. Results: This study describes for the first time the expression, regulation and secretion of pHp and its receptor CD163 in the human lung. The release of soluble mediators from A549 cell line and human monocyte- derived macrophages was observed indicating that Hp dif- ferentially activates the release of soluble mediators and ma- jor chemoattractants. Conclusions: The findings indicate a native function of pHp and CD163 as functional pulmonary defense elements due to local expression, regulation and se- cretion during lung infection and as part of the inflamma- tory immune response of the respiratory system. Copyright © 2011 S. Karger AG, Basel Introduction During the acute phase of inflammatory processes, el- evated expression of acute-phase proteins (APP) is char- acteristic. One of those molecules is hepatic haptoglobin (Hp) occurring in different phenotypes. Its main role is Key Words Acute-phase protein  CD163  Chronic disease  Lung  Haptoglobin  Infection Abstract Background: The acute-phase protein haptoglobin (Hp) and its receptor CD163 serve as immunomodulators and possess anti-inflammatory besides antioxidant functions. Objectives: To further understand the role of the recently described pulmonary Hp (pHp) and its receptor CD163 in case of inflammation and infection, pHp and CD163 were in- vestigated on mRNA and protein level to gain insight into the cellular events taking place upon stimulation with the in- flammatory mediators LPS, Pam3, cytokine IL-6 and dexa- methasone, and upon infection with respiratory pathogens (Haemophilus influenzae, Streptococcus pneumoniae and Chlamydia pneumoniae) by use of a human ex vivo tissue cul- ture model and cell cultures of A549 and alveolar epithelial cells type II. In addition, pHp and CD163 expression in COPD and sarcoidosis was assessed. Methods: We conducted ex- periments using 942 ex vivo cultured lung samples applying immunohistochemistry, immunocytochemistry, in situ hy- Received: September 29, 2010 Accepted after revision: June 1, 2011 Published online: August 22, 2011 Daniel Kähler Clinical and Experimental Pathology, Research Center Borstel Parkallee 3a DE–23845 Borstel (Germany) Tel. +49 4537 188 297, E-Mail dkaehler  @  fz-borstel.de © 2011 S. Karger AG, Basel 0025–7931/12/0831–0061$38.00/0 Accessible online at: www.karger.com/res