Collectins and Viral Infections

 Collectin is an animal lectin, which was found by Kawasaki's group in 1980 as a counter part of plant lectins (1). In 1989 Super found that a deficiency of animal serum lectin (mannose-binding lectin-MBL) is associated with susceptibility to microbial infections in infants, indicating that lectins play an important role in innate immunity. These lectins, which were called collectins, have a collagen-like domain and a carbohydrate recognition domain (CRD). One group of collectins, the secreted lectins consists of mannose-bindin lectin (MBL), bovine conglutinin (BKg), and collectin 43 (CL-43) in blood and the surfactant protein A (SP-A) and surfactant protein D (SP-D) in surfactant fluid and amniotic fluid. The other group consists of the newly found non-secreted type collectin liver-1 and 2 (CL-L1, CL-L2) and membrane type collectin placenta-1 (CL-P1).

In vitro experiments show that the secreted type collectins have three kinds of anti-viral activity (2).

(1) They act like neutralizing antibody and inhibit viral attachment or viral growth in infected cells (direct viral inhibition).
(2) They bind to the glycoproteins and glycolipids on virion or viral anitigens on infected cells and activate the lectin and complement pathway, finally causing the virolysis and cell lysis (the complement activation pathway).
(3) They bind to the glycoproteins and glycolipids on virion or viral antigens on infected cells, and the virion and infected cells are endocytosed via the collectin receptor, the complement receptor, and the C1q receptor in phagocytes (the opsonization pathway).

There is no direct evidence that collectins play a significant role in host defense in the association between viral infections and MBL deficiency. (There are many reports concerning in HIV, HBV and HCV.) The most interesting reports come from experiment gene-targeting experiments in mice (SP-A and D). Previous in vitro experiments indicated that SP-D could play an important role in pulmonary infections. The SP-D knock-out mice manifested an abnormality of homeostasis in lipid metabolism but no susceptibility to pulmonary infections. On the other hand, the SP-A knock-out mice showed susceptibility to pulmonary infections. Since mice have two MBL genes, double knock-out mice are needed to elucidate their role in infection.

The most important and significant report notes that MBL given to MBL-deficient humans was very effective in overcoming susceptibility to infections (3). Although a two-year-old girl was very sick and had been in hospital from four months of age, she became healthy for three years after several injections of MBL. These data indicate that in the future MBL will be a useful drug for immunodeficient persons and will play an important role in resistance to viral or bacterial infections.
Figure legend: Anti-viral activities in collectins
Nobutaka Wakamiya M.D.
(Asahikawa Medical College, Faculty of Medicine)
References (1) Kawasaki T: Structure and biology of mannan-binding protein, MBP, an important component of innate immunity. Biochim. Biophys. Acta 1473(1), 186-95, 1999
(2) Wakamiya N, Suzuki Y, Tanpakushitsu Kakusan Koso 45(5), 655-63, 2000
(3) Valdimarsson H, Stefansson M, Vikingsdottir T, Arason GJ, Koch C, Thiel S, Jensenius, JC: Reconstitution of opsonizing activity by infusion of mannan-binding lectin (MBL) to MBL-deficient humans. Scand. J. Immunol. 48(2), 116-23, 1998
Dec. 15, 2000

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