Pulmonary collectins enhance phagocytosis of Mycobacterium avium through increased activity of mannose receptor.
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 Ca(2+)-dependent but that of SP-D and MBL was Ca(2+)-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 Ca(2+). The mutated collectin, SP-A(E195Q, 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 (125)I-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.
Kudo
Kazumi
K
Department of Biochemistry, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
Sano
Hitomi
H
Takahashi
Hiroki
H
Kuronuma
Koji
K
Yokota
Shin-ichi
S
Fujii
Nobuhiro
N
Shimada
Ken-ichi
K
Yano
Ikuya
I
Kumazawa
Yoshio
Y
Voelker
Dennis R
DR
Abe
Shosaku
S
Kuroki
Yoshio
Y
D000818:Animals; D037222:Collectins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008168:Lung / Q000737:chemistry; D008264:Macrophages / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology; D000090323:Mannose Receptor; D037601:Mannose-Binding Lectin / Q000378:metabolism / Q000502:physiology; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology; D009162:Mycobacterium avium / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism / Q000502:physiology; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015854:Up-Regulation
D037222:Collectins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037601:Mannose-Binding Lectin; D037241:Mannose-Binding Lectins; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011956:Receptors, Cell Surface