A soluble mannose receptor immunoadhesin enhances phagocytosis of Pneumocystis carinii by human polymorphonuclear leukocytes in vitro.
Pneumocystis carinii is an opportunistic pathogen that causes pneumonia in immunocompromised hosts. In the normal host, P. carinii is susceptible to an array of first line host defense mechanisms that are operative in the lung. Alveolar macrophages play a central role in the clearance of inhaled organisms. The macrophage mannose receptor (MR) appears to be sufficient for P. carinii phagocytosis. In individuals infected with the human immunodeficiency virus, MR expression on alveolar macrophages and P. carinii phagocytosis are decreased, however, Fc-receptor mediated phagocytosis remains intact. In this study, we demonstrate that a recombinant soluble MR immunoadhesin, consisting of the essential carbohydrate binding MR ectodomain and the Fc-region of human immunoglobulin (Ig)G1, binds P. carinii and leads to an 8.2-fold increased uptake of P. carinii by phagocytic cells. Our results suggest that the soluble MR immunoadhesin may have therapeutic potential in the treatment of P. carinii infections.
Laboratory of Developmental Immunology, MassGeneral Hospital for Children, and Harvard Medical School, Boston, Massachusetts 02114, USA.
S E
SE
Stehle
R A
RA
Rogers
A G
AG
Harmsen
R A
RA
Ezekowitz
D000818:Animals; D001422:Bacterial Adhesion / Q000276:immunology*; D019556:COS Cells; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D037181:Lectins, C-Type; D016676:Macrophages, Alveolar / Q000276:immunology / Q000382:microbiology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D009894:Opportunistic Infections / Q000276:immunology / Q000628:therapy; D010587:Phagocytosis / Q000276:immunology*; D011010:Pneumocystis / Q000276:immunology* / Q000472:pathogenicity; D011020:Pneumonia, Pneumocystis / Q000276:immunology / Q000628:therapy; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
D007141:Immunoglobulin Fc Fragments; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins