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Titolo:
NONOPSONIC BINDING OF MYCOBACTERIUM-TUBERCULOSIS TO HUMAN-COMPLEMENT RECEPTOR-TYPE-3 EXPRESSED IN CHINESE-HAMSTER OVARY CELLS
Autore:
CYWES C; GODENIR NL; HOPPE HC; SCHOLLE RR; STEYN LM; KIRSCH RE; EHLERS MRW;
Indirizzi:
UNIV CAPE TOWN,SCH MED,DEPT MED BIOCHEM ZA-7925 OBSERVATORY SOUTH AFRICA UNIV CAPE TOWN,SCH MED,DEPT MED BIOCHEM ZA-7925 OBSERVATORY SOUTH AFRICA UNIV CAPE TOWN,SCH MED,DEPT MED MICROBIOL ZA-7925 OBSERVATORY SOUTH AFRICA UNIV CAPE TOWN,SCH MED,DEPT MED ZA-7925 OBSERVATORY SOUTH AFRICA UNIV CAPE TOWN,SCH MED,MRC,LIVER RES CTR CAPE TOWN 7925 SOUTH AFRICA
Titolo Testata:
Infection and immunity
fascicolo: 12, volume: 64, anno: 1996,
pagine: 5373 - 5383
SICI:
0019-9567(1996)64:12<5373:NBOMTH>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTEGRIN MAC-1 CD11B/CD18; MACROPHAGE-DERIVED COMPLEMENT; ALVEOLAR MACROPHAGES; LEUKOCYTE INTEGRINS; MAMMALIAN-CELLS; HUMAN-MONOCYTES; CR3 CD11B/CD18; BETA-SUBUNIT; PHAGOCYTOSIS; ADHESION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
C. Cywes et al., "NONOPSONIC BINDING OF MYCOBACTERIUM-TUBERCULOSIS TO HUMAN-COMPLEMENT RECEPTOR-TYPE-3 EXPRESSED IN CHINESE-HAMSTER OVARY CELLS", Infection and immunity, 64(12), 1996, pp. 5373-5383

Abstract

Nonopsonic invasion of mononuclear phagocytes by Mycobacterium tuberculosis is likely important in the establishment of a primary infectionin the lung. M. tuberculosis binds to a variety of phagocyte receptors, of which the mannose receptor and complement receptor type 3 (CR3) may support nonopsonic binding, CR3, a beta(2) integrin, is a target for diverse intracellular pathogens, but its role in nonopsonic bindingremains uncertain. We have examined the binding of M. tuberculosis H37Rv to human CR3 heterologously expressed in Chinese hamster ovary (CHO) cells, thereby circumventing the problems of competing receptors and endogenously synthesized complement, which are inherent in studies with mononuclear phagocytes, The surface expression of CD11b and CD18,vas assessed by immunofluorescence, immunobead binding, flow cytometry,and immunoprecipitation with anti-CD11b and anti-CD18 monoclonal antibodies (MAbs). The functional activity of the surface-expressed CD11b/CD18 (CR3) heterodimer was confirmed by resetting with C3bi-coated microspheres. We found that M. tuberculosis bound four- to fivefold more avidly to CR3-expressing CHO cells than to wild-type cells and, importantly, that this binding was at similar levels in the presence of fresh or heat-inactivated human or bovine serum or no serum, In contrast, Mycobacterium smegmatis bound poorly to CR3-expressing CHO cells in the absence of serum, but after opsonization in serum, binding was comparable to that of M. tuberculosis. The binding of M. tuberculosis to the transfected CHO cells,vas CR3 specific, as it was inhibited by anti-CR3 MAbs, particularly the anti-CD11b MAbs LM2/1 (I domain epitope) and OKM1 (C-terminal epitope), neither of which inhibit C3bi binding. MAb 2LPM19c, which recognizes the C3bi-binding site on CD11b, had littleor no effect on M. tuberculosis binding. The converse was found for the binding of opsonized M. smegmatis, which was strongly inhibited by 2LPM19c but unaffected by LM2/1 or OKM1, CR3-specific binding was alsoevidenced by the failure of M. tuberculosis to bind to CHO cells transfected with an irrelevant surface protein (angiotensin-converting enzyme) in the presence or absence of serum. We conclude that the bindingof M. tuberculosis H37Rv to CR3 expressed in CHO cells is predominantly nonopsonic and that the organism likely expresses a ligand that binds directly to CR3.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 23:24:27