The matrix metalloproteinases (MMPs) collagenase, gelatinase A (72 kDa gelatinase), stromelysin, and their specific inhibitor TIMP-1 (tissue inhibitor of metalloproteinases), were immunolocalized using specific polyclonal antisera in gingival tissues from 21 patients with chronic inflammatory periodontal disease. Monoclonal antibodies against macrophages (Leu-M5), B cells (Leu-14), helper T cells (OKT4), suppressor T cells (OKT8) and the HLA-DR epitope were also used to identify leukocyte subsets. MMPs were observed in connective tissues at sites that histologically showed signs of remodelling. The number and distribution of positive cells varied widely, however, not only between individual biopsy specimens, but also within the same specimen. The same was true for the composition and distribution of the inflammatory cell infiltrate. Moreover, although there was a positive correlation between the number of MMP-producing cells and the severity of inflammation in some specimens, for others with comparable leukocyte subset scoring the number was reduced and sometimes absent altogether. Cells secreting MMPs were fibroblasts, macrophages and epithelial cells. It was not possible to determine unequivocally whether a MMP-positive cell within the connective tissue was a fibroblast or a macrophage, since the antisera recognise both fibroblast and macrophage MMPs and the different fixation requirements for MMPs (4% paraformaldehyde) and Leu-M5 (acetone) precluded co-localization on the same section. TIMP-1 was immunolocalized within connective tissue cells at sites of tissue remodelling. Our results support the hypothesis that tissue-derived MMPs may be involved in tissue remodelling in periodontal disease and conclusively demonstrate that epithelial cells may be involved as well as connective tissue cells.

Ricin is a toxin and seed protein produced by the castor oil plant, Ricinus communis. The toxin is a dimeric protein consisting of an enzymic A chain and a B chain with lectin properties aiding the uptake of the whole molecule into cells. Ricin has been considered a possible military threat for several decades and is now also of some concern as a terrorist agent. The inhalation route is of primary concern in these situations, although previous attacks with ricin have used other approaches. Medical countermeasures against ricin are urgently required and the strategy adopted has been first to understand the nature of the problem, in this case the inhalation toxicology of ricin, followed by the preparation of vaccine antigens. Toxoided ricin and modified recombinant A chain components have been examined in terms of efficacy as potential vaccine candidates in protection of animal models against inhaled ricin, primarily in laboratories both in the United Kingdom and in the United States. One recombinant A chain vaccine has been taken through to clinical trials in the United States and should become commercially available in the next few years. Toxoided ricin has also been used as an antigen to prepare antitoxin antibodies for therapeutic treatment following poisoning. In this review, a synopsis of the inhalation toxicology of ricin and approaches to medical prophylaxis and therapy of poisoning is given, based on work conducted at our laboratory and at other research institutes.

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Ricin toxin, a type 2 ribosome inactivating protein and a category B bioterrorism agent, is produced from the seeds of castor oil plant (Ricinus communis). Chronic pathological changes in survivors of aerosolized ricin exposure have not been reported in primates. Here we compare and contrast the pathological changes manifested between rhesus macaques (RM) that succumbed to lethal dose of ricin (Group I) and survivor RM exposed to low dose of ricin (group II). All animals in group I exhibited severe diffuse, necrotizing bronchiolitis and alveolitis with fibrinopurulent bronchointerstitial pneumonia, massive alveolar, perivascular and peribronchial/bronchiolar edema with hemorrhage and necropurulent and hemorrhagic tracheobronchial lymphadenitis. All animals from groups II had multifocal, fibrosing interstitial pneumonia with prominent alveolar histiocytosis and type II pneumocyte hyperplasia. Subacute changes like infiltration by lymphocytes and plasma cells and persistence of edematous fluid were occasionally present in lung and tracheobronchial lymph nodes. The changes appear to be a continuum wherein the inflammatory response shifts from an acute to subacute/chronic reparative process if the animals can survive the initial insult.

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