The status of IPF in the Japanese population was clarified for the first time through our study. Our results showed that in men, the incidence of death caused by acute exacerbation was higher and that caused by cardiovascular disease was lower in Japan than in Western countries. These results may suggest ethnic differences in IPF.

The lung collectin surfactant protein A (SP-A) has been implicated in the regulation of pulmonary host defense and inflammation. Zymosan induces proinflammatory cytokines in immune cells. Toll-like receptor (TLR)2 has been shown to be involved in zymosan-induced signaling. We first investigated the interaction of TLR2 with zymosan. Zymosan cosedimented the soluble form of rTLR2 possessing the putative extracellular domain (sTLR2). sTLR2 directly bound to zymosan with an apparent binding constant of 48 nM. We next examined whether SP-A modulated zymosan-induced cellular responses. SP-A significantly attenuated zymosan-induced TNF-α secretion in RAW264.7 cells and alveolar macrophages in a concentration-dependent manner. Although zymosan failed to cosediment SP-A, SP-A significantly reduced zymosan-elicited NF-κB activation in TLR2-transfected human embryonic kidney 293 cells. Because we have shown that SP-A binds to sTLR2, we also examined whether SP-A affected the binding of sTLR2 to zymosan. SP-A significantly attenuated the direct binding of sTLR2 to zymosan in a concentration-dependent fashion. From these results, we conclude that 1) TLR2 directly binds zymosan, 2) SP-A can alter zymosan-TLR2 interaction, and 3) SP-A down-regulates TLR2-mediated signaling and TNF-α secretion stimulated by zymosan. This study supports an important role of SP-A in controlling pulmonary inflammation caused by microbial pathogens.

Collectins, including surfactant proteins A (SP-A) and D (SP-D) and mannose binding lectin (MBL), are the important constituents of the innate immune system. Mycobacterium avium, a facultative intracellular pathogen, has developed numerous mechanisms for entering mononuclear phagocytes. In this study, we investigated the interactions of collectins with M. avium and the effects of these lectins on phagocytosis of M. avium by macrophages. SP-A, SP-D, and MBL exhibited a concentration-dependent binding to M. avium. The binding of SP-A to M. avium was Ca2+-dependent but that of SP-D and MBL was Ca2+-independent. SP-A and SP-D but not MBL enhanced the phagocytosis of FITC-labeled M. avium by rat alveolar macrophages and human monocyte-derived macrophages. Excess mannan, zymosan, and lipoarabinomannan derived from the M. avium-intracellular complex, significantly decreased the collectin-stimulated phagocytosis of M. avium. Enhanced phagocytosis was not affected by the presence of cycloheximide or chelation of Ca2+. The mutated collectin, SP-AE195Q, R197D exhibited decreased binding to M. avium but stimulated phagocytosis to a level comparable to wild-type SP-A. Enhanced phagocytosis by cells persisted even after preincubation and removal of SP-A or SP-D. Rat alveolar macrophages that had been incubated with SP-A or SP-D also exhibited enhanced uptake of 125I-mannosylated BSA. Analysis by confocal microscopy and flow cytometry revealed that the lung collectins up-regulated the cell surface expression of mannose receptor on monocyte-derived macrophages. These results provide compelling evidence that SP-A and SP-D enhance mannose receptor-mediated phagocytosis of M. avium by macrophages.

Pulmonary surfactant proteins A (SP-A

Pulmonary surfactant proteins (SP) A and D play important roles in the innate immune system of the lung. These proteins belong to the collectin subgroup in which lectin domains are associated with collagenous structures. To obtain a better understanding of how lung collectins modulate cellular responses, the authors investigated whether SP-A interacts with the toll-like receptor 2 (TLR2). SP-A bound to TLR2 and inhibited interactions between TLR2 and TLR2-ligands such as peptidoglycan (PGN) and zymosan. NF-κ B activation and tumour necrosis factor-α expression induced by PGN or zymosan were significantly inhibited in the presence of SP-A. Lung collectins may act as inhibitors of lung inflammation in respiratory infections. The authors also examined the effects of lung collectins on the phagocytosis of bacteria by alveolar macrophages. Lung collectins enhanced the uptake of S. pneumoniae or M. avium by alveolar macrophages. It was demonstrated that the direct interaction of lung collectins with macrophages resulted in increased cell surface expression of scavenger receptor A or mannose receptor, which are responsible for phagocytosis. This study has emphasized the biological relevance of SP-A and SP-D against various respiratory infections, however, a more complete understanding of the molecular mechanism is required.

Keywords: pigeon for race, bird-related hypersensitivity pneumonitis, interstitial pneumonia, hypersensitivity pneumonitis,

We determined the most important thing for a public library to have is a room that provides visitors with a comfortable space in which to read. For this project, we proposed a simple space measuring 45 3 45 m, with a height of about 12 m, enclosed by a "punching wall" supported by 25 pillars. The overall structure of the library consists of an internal layer of three floors covered with a large box referred to as a "cake box". The reading room is supported by steel braces hidden in the walls, and has about 6000 round windows, and thin round pillars around the room. In addition, an air conditioning system that warms and cools the building was installed under the floor in order to make the space comfortable to inhabit, while large natural ventilation openings in the roof ensure a pleasant indoor environment during the warmer months.