The Journal of Experimental Medicine
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Published online 18 December 2000.
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© The Rockefeller University Press, 0022-1007/2000/12/1797/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 12, December 18, 2000 1797-1808

Original Article

Complement Receptor 1/CD35 Is a Receptor for Mannan-binding Lectin

Ionita Ghirana, Sergi F. Barbashova, Lloyd B. Klicksteinb, Sander W. Tasa, Jens C. Jenseniusc, and Anne Nicholson-Wellera
a Harvard-Thorndike Laboratory, Division of Allergy and Inflammation, and the Division of Infectious Disease, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215
b Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
c Department of Medical Microbiology and the Department of Immunology, University of Aarhus, Aarhus 8000, Denmark

Correspondence to: Anne Nicholson-Weller, Beth Israel Deaconess Medical Center, Dana Bldg. 617, 330 Brookline Ave., Boston, MA 02215. Tel:617-667-3307 Fax:617-277-6061 E-mail:anichols{at}caregroup.harvard.edu.

Mannan-binding lectin (MBL), a member of the collectin family, is known to have opsonic function, although identification of its cellular receptor has been elusive. Complement C1q, which is homologous to MBL, binds to complement receptor 1 (CR1/CD35), and thus we investigated whether CR1 also functions as the MBL receptor. Radioiodinated MBL bound to recombinant soluble CR1 (sCR1) that had been immobilized on plastic with an apparent equilibrium dissociation constant of 5 nM. N-acetyl-D-glucosamine did not inhibit sCR1–MBL binding, indicating that the carbohydrate binding site of MBL is not involved in binding CR1. C1q inhibited MBL binding to immobilized sCR1, suggesting that MBL and C1q might bind to the same or adjacent sites on CR1. MBL binding to polymorphonuclear leukocytes (PMNs) was associated positively with changes in CR1 expression induced by phorbol myristate acetate. Finally, CR1 mediated the adhesion of human erythrocytes to immobilized MBL and functioned as a phagocytic receptor on PMNs for MBL–immunoglobulin G opsonized bacteria. Thus, MBL binds to both recombinant sCR1 and cellular CR1, which supports the role of CR1 as a cellular receptor for the collectin MBL.

Key Words: C1q, opsonins, neutrophil, erythrocyte, innate immunity


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