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A B S T R A C T Alveolar macrophages are the initial phagocytic cells that encounter foreign material and particulates deposited in the terminal airways. We have examined a mechanism by which these cells, after phagocytic challenge, may control or amplify the inflammatory response in lung parenchyma. Normal human alveolar macrophages (AM) were studied from eight subjects. With in vitro culture, AM produced and released two substances into culture media which have potent chemoattractant activity for blood polymorphonuclear granulocytes(PMN) and negligible activity for mononuclear cells. Release of these factors is maximally stimulated by aggregated human immunoglobulin (Ig)G or zymosan particles; however, simple adhesion of the macrophages to plastic surfaces is also sufficient to stimulate release of these chemotactic substances.The larger substance (10,000 daltons) is immunologically distinct from C5a and interacts with a different PMN membrane receptor than that known to exist for formyl-methionyl-leucyl-phenylalanine. Its chemotactic activity is sensitive to the enzymatic effect of trypsin. Although producing a single elution peak on gelfiltration chromatography, electrofocusing in polyacrylamide gels yielded five peaks of radioactivity. Chemotactic activity was localized to a fraction with a pI = 5.0. The smaller molecular weight substance has been less well characterized. Thus, the human AM can produce at least two factors which attract PMN and this capability may augment the local inflammatory response in the lung.

A B S T R A C T Pseudomonas aeruginosa infection plays a primary pathogenetic role in the chronic respiratory tract disease of cystic fibrosis (CF) patients. Despite pronounced humoral immune responses, reflected by high levels of antibodies against Pseudomonas in serum and in sputum, the antibodies do not eliminate this bacterium. In the present study we have used affinity chromatography with a lipopolysaccharide substituted immunoadsorbent gel to isolate high titers (meanCF = 1:256) of immunotype specific Pseudomonas IgG antibodies from the sera of nine CF subjects, and have evaluated the functional ability of these antibodies to promote phagocytosis and intracellular killing of P. aeruginosa in an in vitro human alveolar macrophage culture system.The phagocytic and intracellular bactericidal kinetics revealed that CF IgG antibodies function in an inhibitory fashion. Both the rate of phagocytosis (rateCF = 204 cpm/unit time) and absolute bacterial uptakes maximal at 120 min (uptakecF = The cellular and humoral immune systems in subjects with CF appear to function normally (1, 3-5) with one major exception: whole serum appears to interfere with the phagocytic function of alveolar macrophages (AM). Whole serum from homozygous CF patients inhibits the ability of rabbit and human AM to ingest and destroy Pseudomonas bacteria (6-9). This effect has been variously attributed to a serum deficiency, to a heat-labile factor, or more recently, to a heat-stable inhibitory factor in CF sera (6-9). "Bactericidal blocking" antibodies have been suggested as an explanation for the selective inability of CF whole serum to support Pseudomonas bactericidal activity (10).Optimal phagocytosis of Pseudomonas by polymorphonuclear leukocytes (PMN) or AM requires the presence of heat-stable opsonins (11,12), and of the heat-stable opsonins IgG has superior protective activity when compared with secretory IgA or . Murphy et al. (15) have studied the role of complement in the phagocytosis of Pseudomonas by rabbit AM. These authors concluded that specific antibody is required for efficient phagocytosis but that in the presence of an excess amount of antibody (as in CF) complement was not essential to maximize phagocytosis. Similarly, IgG antibodies in convalescent sera have been shown to augment phagocytosis of Pseudomonas even in the absence ofheat-labile (complement) opsonins (16,17). Because of the importance of immune IgG in the phagocytic process, and special constraints in antibody binding to macrophages imposed by specific cell surface receptors (18), it is likely that such an opsonic antibody deficiency would be in the IgG class.While CF patients have a generous antibody response in serum, sputum, and to a lesser degree, in lung lavage fluid to P. aeruginosa somatic antigens, the functional capacity of these specifically purified antibodies has not been studied directly. To investigate the opsonic, phagocytic, and bactericidal properties of P. aeruginosa lipopolysaccharide type-specific IgG opsonins (Pseudomonas antibodies), w...

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The purpose of this study was to examine the relationship between immunoglobulin production and immunoglobulin levels in bronchoalveolar lavage (BAL) fluid and serum of normal subjects and patients with sarcoidosis. Eleven normal volunteers and 17 patients were studied. In normal subjects, no important relationship existed between the number of immunoglobulin-secreting cells and immunoglobulin levels in BAL or serum. By contrast, in patients with sarcoidosis, a highly significant correlation existed between the number of IgG secreting cells and IgG/alb% in BAL (p = 0.008) and between the number of IgG secreting cells in BAL and serum IgG mg/ml (p = 0.002). Similar associations did not exist for IgA and IgM. These data demonstrate for the first time the relationship between immunoglobulin production and immunoglobulin levels in normal persons, and convincingly show that immunoglobulin production at sites of disease activity is responsible for hypergammaglobulinemia in BAL and serum of patients with sarcoidosis.