Identification of the leukocyte adhesion molecules CD11 and CD18 as receptors for type 1-fimbriated (mannose-specific) Escherichia coli.
Attachment of bacteria to phagocytic cells may be mediated by lectin-carbohydrate interactions, resulting in lectinophagocytosis. The best-studied system is the interaction of type 1-fimbriated (mannose-specific) Escherichia coli with human phagocytic cells. Here we demonstrate that the leukocyte integrins CD11 and CD18 (CD11/CD18) constitute the major receptors for type 1-fimbriated E. coli. Bacteria were bound in a dose-dependent and saturable manner to CD11/CD18, which was immobilized to microwells, whereas nonfimbriated E. coli cells failed to bind. The binding was efficiently inhibited (82 to 85%) by methyl-alpha-mannoside but not by galactose, and it was reduced by treatment of the immobilized CD11/CD18 with sodium metaperiodate, endoglycosidase H, or a mixture of endoglycosidase F and N-glycosidase. The fimbriated bacteria also bound to CD11a,b,c and CD18 separated by polyacrylamide gel electrophoresis with sodium dodecyl sulfate and blotted onto nitrocellulose paper. This binding was inhibited specifically by methyl-alpha-mannoside and was significantly diminished by treatment of the blots with sodium metaperiodate. Only minimal binding to the blotted CD11/CD18 that had been deglycosylated enzymatically prior to electrophoresis was observed. On blots of granulocyte lysates, specific binding to two glycoproteins (Mrs, 90,000 to 100,000 and 165,000) with mobilities similar to that of CD11/CD18 was observed. Monoclonal antibodies to CD11a, CD11b, or CD18 inhibited the binding of the bacteria to intact human granulocytes by 55 to 80%, whereas antibodies against other leukocyte surface antigens were not inhibitory. We conclude that type 1-fimbriated E. coli binds to human granulocytes via the oligomannose and hybrid N-linked units of CD11/CD18. Since CD11b/CD18 and CD11c/CD18 are known to serve as receptors for complement fragment iC3b, this study provides a link between opsonophagocytosis and lectinophagocytosis.
Department of Biophysics, Weizmann Institute of Science, Rehovot, Israel.
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A
Gbarah
C G
CG
Gahmberg
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I
Ofek
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U
Jacobi
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Sharon
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D001422:Bacterial Adhesion; D018845:CD11 Antigens; D018821:CD18 Antigens; D004926:Escherichia coli / Q000502:physiology*; D010861:Fimbriae, Bacterial / Q000502:physiology; D008358:Mannose / Q000378:metabolism*; D008970:Molecular Weight; D010587:Phagocytosis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D008358:Mannose