Regulation of inflammation and bacterial clearance by lung collectins.
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-kappaB activation and tumour necrosis factor-alpha 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.
Sano
Hitomi
H
Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo, Japan. sanohito@sapmed.ac.jp
Kuronuma
Koji
K
Kudo
Kazumi
K
Mitsuzawa
Hiroaki
H
Sato
Morihito
M
Murakami
Seiji
S
Kuroki
Yoshio
Y
D000818:Animals; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology; D009162:Mycobacterium avium / Q000276:immunology; D010587:Phagocytosis / Q000502:physiology; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000276:immunology; D051117:Scavenger Receptors, Class A / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*
D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011956:Receptors, Cell Surface; D051117:Scavenger Receptors, Class A; D051195:Toll-Like Receptor 2