Surface receptors of neutrophils towards B. burgdorferi.
The spirochetal agent of Lyme borreliosis, Borrelia burgdorferi, is able to induce an infection which develops in three stages: an early, localized infection, disseminated infection and a third stage, chronic infection, which probably indicates that a protected niche has been established in one or more tissues, where the spirochetes persist even if a specific immune response has been initiated. During the first stage, immediately after their entry into the host tissue, B. burgdorferi meet the motile phagocytic cells, neutrophils and monocytes; this is followed by consequent phagocytosis and killing. Although the rate and mechanism of this killing is not entirely clear, there is evidence that phagocytosis by both neutrophils and monocytes proceeds even in the absence of specific antibodies. We have demonstrated in both neutrophils and CHO Mac-1 (CR3 integrin) transfected cells, that one phagocyte receptor which is involved in B. burgdorferi adhesion in non osponic phagocytosis is the CR3 complement receptor known as integrin alpha m beta 2. Both recognition domains of the integrin, the iC3b site and the COOH terminal lectin site, bind to B. burgdorferi. Data presented here show that inhibition of adhesion on CR3 Mac-1 transfected cells and neutrophils is induced by mannose as well as by N-acetyl-D-glucosamine, sugars known to be specific inhibitors of the COOH terminal lectin-site of the integrin CR3. The inhibitory effect was serum complement independent. On the contrary, monoclonal antibody VIM12 directed towards the lectin domain not only failed to inhibit but improved adhesion, suggesting that, as a consequence of the binding, the integrin becomes more receptive to B. burgdorferi attachment at the I domain. Pretreatment of the borrelias with NalO4 eliminated adhesion, suggesting that the sugar residue/s recognized by CR3 is located on the bacteria.
Dipartimento di Scienze Biomediche, Sez. Microbiologia, Università di Trieste, Italy. Cinco@fc.Univ.Trieste.it
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Murgia
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Perticarari
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015748:Borrelia burgdorferi Group / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016466:CHO Cells; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D006224:Cricetinae; D006801:Humans; D016177:Macrophage-1 Antigen / Q000097:blood / Q000276:immunology; D008358:Mannose / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D010504:Periodic Acid / Q000494:pharmacology; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D011971:Receptors, Immunologic / Q000097:blood*; D011975:Receptors, Mitogen / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D008934:Mitogens; D011971:Receptors, Immunologic; D011975:Receptors, Mitogen; D010504:Periodic Acid; C009288:metaperiodate; D008358:Mannose