['macrophage', 'death', 'might', 'ensue', 'or', 'the', 'macrophages', 'might', 'secrete', 'potent', 'pro-', 'teases,', 'fatty', 'acids', 'or', 'cytolytic', 'factors,', 'which', 'could', 'lead', 'to', 'death,', 'de~', 'struction', 'or', 'hyperplasia', 'of', 'pulmonary', 'epithelial', 'cells,', '3.0', 'EXPERIMENTAL', 'PLAN', 'OF', 'ATTACK', 'We', 'have', 'already', 'demonstrated', 'preliminarily', 'that', 'environmental', 'par-', 'ticles,', 'naturally', 'coated', 'with', 'soil-derived', 'organic', 'materials', 'or', 'experi-', 'mentally', 'coated', 'with', 'respirable', 'smoke,', 'can', 'be', 'injurious', 'to', 'Macrophages', 'or', '‘alter', 'some', 'of', 'their', 'functions', '(i.e.', 'secretion', 'of', 'CF).', 'We', 'now', 'wish', 'to', 'define', 'the', 'functions', 'of', 'macrophage', 'altered', 'by', 'exposure', 'to', 'various', 'coated', 'environmental', 'particle?', 'Our', 'first', 'goal', 'will', 'be', 'to', 'assess', 'the', 'specificities', 'of', 'the', 'inter-', 'actions', 'described', 'in', 'this', 'hypothesis:', '(1)', 'What', 'are', 'the', 'specificities,', 'if', 'any,', 'in', 'the', 'altered', 'function(s)', 'of', 'macrophages', 'produced', 'by', 'cleansed', 'and', 'coated', 'silicious', 'par-', "'.", 'ticles?', '(2)', 'What', 'are', 'the', 'specificities,', 'if', 'any,', 'in', 'regard', 'to', 'the', 'type', 'of', 'macrophages?', '(i.e.,', 'do', 'alveolar', 'macrophages', 'from', 'various', 'species', 'respond', 'similarly?', 'Do', 'peritoneal', 'and', 'alveolar', 'macrophages', 'respond', 'similarly?', 'Do', 'cells', 'elicited', 'or', 'activated', 'in', 'vivo', 'by', 'various', 'agents,', 'e.g.,', 'thioglycolate,', "Freund's", 'adjuvant,', 'etc.,', 'respond', 'si-', 'milarly?)', '(3)', 'What', 'are', 'the', 'specificities,', 'if', 'any,', 'in', 'the', 'altered', 'functions', 'produced', 'by', 'different', 'organic', 'contaminants', 'and', 'different', 'par-', 'ticles?', 'For', 'example,', 'since', 'both', 'pyrolyzed', '(smoke)', 'and', 'non-pyro-', 'lyzed', '(endotoxin)', 'organic', 'materials', 'can', 'trigger', 'CF', 'secretion', 'by', 'peritoneal', 'macrophages,', 'it', 'appears', 'that', 'the', 'organic', 'contaminants', 'may', 'not', 'be', 'chemically', 'specific.', 'Our', 'second', 'goal', 'is', 'to', 'study', 'the', 'interaction', 'of', 'macrophages', 'exposed', 'to', 'environmental', 'particles', 'with', 'other', 'cells', 'of', 'the', 'lung', 'such', 'as', 'Type', 'ITI', 'cells', 'or', 'fibroblasts.', 'Using', 'already', 'established', 'culture', 'of', 'these', 'cells', 'obtained', 'from', 'different', 'species', '(human,', 'rat', 'and', 'rabbit)', 'as', 'targets,', 'we', 'will', 'test', 'the', 'cytotoxic', 'effects', 'of', 'the', 'stimulated', 'Macrophages', 'and', 'of', 'their', 'secretions.', ';', 'These', 'studies', 'in', 'vitro', 'are', 'designed’', 'to', 'serve', 'as', 'a', 'prelude', 'to', 'studies', 'in', 'vivo.', 'Since', 'the', 'cost', 'of', 'animal', 'exposure', 'to', 'inhaled', 'pollutants', 'is', 'extremely', 'high,', 'we', 'propose', 'to', 'use', 'the', 'in', 'vitro', 'studies', 'as', 'screens.', 'We', 'will', 'determine', 'the', 'critical', 'combinations', 'of', 'particles', 'and', 'contaminants', 'that', 'lead', 'to', 'critical', 'alterations', 'in', 'the', 'function', 'of', 'macrophages.', 'Once', 'we', 'have', 'established', 'this', 'information,', 'we', 'will', 'test', 'our', 'hypothesis', 'in', 'vivo.', 'We', 'anticipate', 'that', 'the', 'critical', 'combinations', 'of', 'particles', 'and', 'contaminants,', 'when', 'administered', 'in', 'vivo,', 'will', 'produce', 'the', 'critical', 'alterations', 'in', 'macro-', 'phages.', ' ', '12', '50216675']