ABSTRACT
Interaction between Aspergillus fumigatus conidia and different proteins known to mediate the attachment of malignant tumor cells or microorganisms to the host tissues was studied in vitro. Flow cytometry using fluorescein isothiocyanate-conjugated fibrinogen confirmed that binding of human fibrinogen to the conidia was dose dependent and specific. Binding was inhibited by unlabeled fibrinogen and by basement membrane laminin. Moreover, the expression of fibrinogen receptors at the surfaces of conidia seemed to be related to the maturation of the conidia. Binding sites appeared to be located in the D domains of the fibrinogen molecule. However, the peptide sequence recognized by the fungus could not be identified but was different from the classical adhesive recognition sequences, RGDS and fibrinogen gamma-chain dodecapeptide. In addition, an assay of adherence to proteins immobilized onto microtiter plates allowed us to establish the role of these interactions in fungal adhesion. Conidia strongly adhered to human fibrinogen and to laminin but not to fibronectin. Adhesion to fibrinogen substrates was specific, since it was inhibited by soluble fibrinogen and by specific antibodies, and seemed to be mediated by the D domains of the molecule. Study of the adhesion of numerous strains or clinical isolates to various mammalian fibrinogens did not reveal any particular affinity of strains for some animal species. Finally, by cultivation of the fungus in the presence of 125I-human fibrinogen and analysis of the radiolabeled material bound to the surface of the fungus, we were able to specify the sequence of events allowing its installation within the host. The interactions identified here may play an important role in governing fungal adherence and host tissue invasion.
Subject(s)
Aspergillus fumigatus/pathogenicity , Fibrinogen/physiology , Binding Sites , Cell Adhesion , Flow Cytometry , Humans , Oligopeptides/physiologyABSTRACT
MRL - lpr/lpr (MRL/l) mice spontaneously develop an autoimmune pathology including arthritic lesions. SR 41319, a bisphosphonate, having previously shown to be active in in vitro and in vivo models of arthritis, the aim of this study was to search for its possible effect on the pathology of the MRL/l mice. Results showed that SR 41319 reduced the severity of the disease in its early stages and increased mean life span. Further investigation would be necessary to define the effect of the drug during later stages when major changes in immune status occurred.
Subject(s)
Autoimmune Diseases/immunology , Diphosphonates/pharmacology , Lupus Erythematosus, Systemic/immunology , Phospholipases A/antagonists & inhibitors , Phospholipases/antagonists & inhibitors , Animals , Autoimmune Diseases/pathology , Lupus Erythematosus, Systemic/pathology , Mice , Mice, Inbred StrainsABSTRACT
Hairless rats with dermatosis induced with a poor magnesium diet were previously shown to bear biochemical and immunological abnormalities. It was therefore felt of interest to investigate the spleen cells proliferative responses from these rats, both in the rash and the remission phases, when testosterone and parathormone plasma levels were also determined. Results showed that proliferative responses to mitogens and PTH levels were inversely related to the intensity of the dermatosis, whereas testosterone levels were more or less decreased. The role of 1.25 dihydroxyvitamin D3 in these modifications is questionable.
Subject(s)
Lymphocyte Activation , Magnesium Deficiency/immunology , Skin Diseases/immunology , Spleen/immunology , Animals , Magnesium Deficiency/blood , Male , Parathyroid Hormone/blood , Rats , Skin Diseases/etiology , Testosterone/bloodABSTRACT
Dermatosis in magnesium-deficient hairless rats has been described as a reproducible model of skin inflammation. It was therefore felt of interest to search for the effects of various anti-inflammatory compounds on this model. Results showed that 1) Dexamethasone acetate completely abolished the rash, 2) Indomethacin, a Non-Steroidal Anti-Inflammatory Drug (NSAID), inhibitor of the cyclooxygenase pathway was quite inactive, 3) Benoxaprofen, a NSAID inhibitor of both cyclooxygenase and lipoxygenase pathways only slightly modified the development of the pathology. Activity of steroidal anti-inflammatory drugs on this model may be related to their immunosuppressive effects.
