Mcp-1 Synthesis By Diisocyanate Antigen Stimulated Pbmcs Is A More Sensitive In Vitro Assay For Diisocyanate Asthma Than Specific Antibodies

VOLUME 109, NUMBER 1 marked expansion of the medulla. To determine whether this local inflammatory reaction non-specifically augmented the entry of peripheral T cells into the thymus, ~-gal immunized mice were injected i.v. with a population of CFSE-labeled CD4+ T cells specific for an unrelated antigen four days after i.t. injection of LBSHG or LXSHG. Animals that received LBSHG had 2.4-fold more CFSE-labeled CD4+ thymic ilnmigrants than animals that received the control vector. Thus, we have established a model of intrathymic inflammation that is based in the thymic medulla and shown that such an inflammatory process promotes the nonspecific entry of peripheral CD4+ T cells into the thymus. Having established AChR-reactive CD4+ T cell lines, we will now use this model to determine whether 1) homing of these autoreactive T cells to the thymus is also augmented by a concurrent intrathymic inflammatory response to an unrelated antigen, 2) AChR-reactive CD4+ T cell immigrants undergo activation following their engagement of autoantigen in this inflammatory milieu and 3) this intrathymic interaction leads to the production of anti-AChR antibodies. 8 ~ Q MCP-1 Synthesis by Diisecyanate Antigen Stimulated PBMCs Is ~ t J I a More Sensitive In Vitro Assay for Diisocyanate Asthma Than Specific Antibodies Zana L Lumrnus*, Andrd Cartier§, Louis-Philippe Boulet~, Johanne C3tgC, Jean-Luc Malo§, Mark Wanner*, Joanne Milot 6 mths). This study indicates that the MCP-I stimulation assay identifies a unique immunologic marker of DA and has superior sensitivity and equivalent specificity to the serum specific IgE antibody assay in correctly classifying workers at risk for DA. 859 Occupational Lung Disease Related to Cytophage Endotoxin Exposure Mark E Nordness, Michael Christian Zacharisen, Jordan N Fink, Donald P Schlueter Medical College of Wisconsin, Milwaukee, WI Endotoxins are lipopolysaccharides found in the outer membrane of gram-negative bacteria and are potent proinflammatory agents. Inhalation of endotoxin has been implicated in the pathogenesis of numerous respiratory diseases including obstructive lung diseases and hypersensitivity pneumonitis. We report the development of hypersensitivity pneumonitis in workers at a large nylon plant after exposure to Cytophaga from the chilled water spray air conditioning system. Cytophaga is an endotoxin containing bacterium not usually implicated in human diseases, Several employees experienced recurrent cough, fever, myalgias and dyspnea with exertion. Symptoms were temporally related with work environment exposure. Chest x-rays showed diffuse nodular infiltrates. Pulmonary function studies demonstrated restrictive defects and decreased diffusing capacity. Cytophaga bacterium were isolated from an air conditioning system slime. Precipitating antibodies were identified against Cytophaga. Lung biopsies performed on seven employees were consistent with hypersensitivity pneumonitis. Inhalation challenges with Cytophaga endotoxin were performed on two employees with proven hypersensitivity pneumonitis, two asymptomatic exposed controls with precipitating antibodies and two nonexposed individuals without precipitating antibodies. Systemic symptoms, including fever, myalgias and leukocytosis, occurred with every subject. Acute and delayed-onset pulmonary function changes were noted with the exposed controls with precipitating antibodies and those with hypersensitivity pneumonitis. Nonexposed controls had only acute pulmonary function changes. Cytophaga bacterium endotoxin antigen is capable of inducing hypersensitivity pneumonitis as well as systemic symptoms in nonsensitized individuals. It may play a role in respiratory diseases related to contaminated HVAC systems. '~ Airborne Endotoxin Is a Significant Determinant of Symptoms in I # I ~ Laboratory Animal Workers Karin A Pacheco*, Cecile S Rose*, Peter S Thorne§, Marsha E O'Neill§, Charles McCammon*, John Martyny*, Lee S Newman*, Richard F Hammany Andrew H Liu* *National Jewish Medical and Research Center, Denver, CO §University of Iowa, Iowa City, IA YUniversity of Colorado, Denver, CO BACKGROUND: From 30-50% of laboratory animal (LA) workers develop symptoms with exposure to laboratory animals, but only half are sensitized to LA. We hypothesized that airborne endotoxin (ET) present in animal care facilities and research laboratories contributes to symptoms associated with workplace exposure to mice. METHODS: We collected 42 side-by-side samples for airborne mouse allergen (MA) and ET in animal care rooms and research laboratories during different tasks. We measured airborne ET using a modified LAL assay, and MA by inhibition ELISA. We administered a modified ATS questionnaire focused on symptoms and work practices to 269/311 (87%) eligible animal handlers and research scientists. We performed prick skin tests (n=253) or RASTs (n=16) to common environmental allergens and to mouse urine and epithelium. We defined mouse sensitized as a positive skin test or RAST to mouse. We defined mouse symptomatic as 1 or more nasal, chest, or skin symptoms reported to mouse. RESULTS: We found ET throughout the animal rooms and research labs. Mean ET was highest in the animal facility experimental rooms at 6 EU/m3, with a peak of 14 EU/m3, and from 2-3 EU/m3 in the animal rooms and cage wash. ET was 1-2 EU/m3 in mouse research labs, and .3-.6 EU/m3 in labs without LA. MA was 179 ng/m3 in dirty cage wash, 39 ng/m3 in experimental rooms, from 34-79 ng/m3 in mouse research labs and 24-35 ng/m3 in non-LA labs. There were 212 non-sensitized workers, and 57 workers sensitized to mice. Symptomatic non-sensitized workers (n=34) were more likely to be atopic or diagnosed with asthma (p