| First Author | Palaniyar N | Year | 2003 |
| Journal | Int J Exp Pathol | Volume | 84 |
| Pages | A67-A68 (Abstr) | Mgi Jnum | J:87338 |
| Mgi Id | MGI:2684528 | Citation | Palaniyar N, et al. (2003) Pulmonary surfactant protein D deficiency leads to altered decorin and TGF-Beta concentrations in the lung. Int J Exp Pathol 84:A67-A68 (Abstr) |
| abstractText | Full text of Abstract: BSMB Spring 2003 Meeting Report. Pulmonary surfactant protein D deficiency leads to altered decorin and TGF-Beta concentrations in the lung. N. PALANIYAR,* E. KIM,* J. NADESALINGAM,* H. CLARK,* S. HAWGOOD+ AND K.B.M. REID*. *MRC Immunochemistry Unit, Department of Biochemistry, Oxford University, Oxford, UK; +Department of Pediatrics and Cardiovascular Research Institute, University of California, San Francisco, CA, USA. Introduction. Surfactant protein D (SP-D) is a collectin present in the lung and other mucosal surfaces, and its absence results in the accumulation of apoptotic macrophages, chronic inflammation, airway remodelling and emphysema in the lung (Botas et al. 1998; Clark et al. 2002). We recently copurified decorin and SP-D from amniotic fluid and showed that these two molecules interact effectively with each other, in vitro (Nadesalingam et al., in press). To test our hypothesis that interactions of decorin with SP-D and TGF-Beta regulate the SP-D-related lung phenotypes, we determined the concentrations of these proteins in the lung lavage obtained from mice. Materials and methods. Lungs of wildtype and gene knockout [SP-A(Ð/Ð) and SP-D(Ð/Ð)] mice (Botas et al. 1998) were washed with saline, and the concentrations of decorin, SP-D and TGF-Beta in the lavage fluid were measured by ELISA. The nature of the TGF-Beta and decorin was determined by Western blot analyses. Results. First, we found that SP-D concentrations increased with increasing age of the mice, whereas the decorin levels decreased. Second, decorin concentration is elevated in the SP-D(Ð/Ð) mice compared with that of SP-A(Ð/Ð) and wildtype mice. Third, Western blot analyses suggest that unprocessed form of TGF-Beta may accumulate in the lung of SP-D(Ð/Ð) mice. Discussion. These results collectively suggest that low concentrations, or the absence, of SP-D lead to an increase in alveolar concentrations of decorin, which in turn may reduce the availability of the active form of TGF-Beta. Because TGF-Beta is known to enhance the clearance of apoptotic macrophages, the reduced levels of the active form of this cytokine may be one of the important factors responsible for less effective clearance and subsequent accumulation of apoptotic macrophages in the SP-D(Ð/Ð) mice lungs. Our results are consistent with the interpretation that the dysfunction of the multilevel regulation of SP-DÐdecorinÐTGF-Beta pathway partly reflects the phenotypes seen in the SP-D(Ð/Ð) mice and includes SP-D as one of the putative regulatory molecules in this pathway. Acknowledgement. This work was partly supported partly by the Wellcome Trust/CIHR (PN), MRC (JN, EK, HC and KBMR), EU (JN and KBMR) and grants HL-24075 and HL58047 from NIH (SH). References BOTAS C., POULAIN F., AKIYAMA J. ET AL. (1998) Proc. Natl. Acad. Sci. U S A 95, 11869-11874. CLARK H., PALANIYAR N., STRONG P., EDMONDSON J., HAWGOOD S. & REID K.B. (2002) J. Immunol. 169, 2892-2899. NADESALINGAM J., LOPEZ BERNAL A., DODDS A.W. ET AL. (2003) J. Biol. Chem. 278, 25678-25687. |
