Specificity of opsonic antibodies to enhance phagocytosis of Pseudomonas aeruginosa by human alveolar macrophages.

Reynolds, Herbert Y.; Kazmierowski, John A.; Newball, Harold H.

doi:10.1172/jci108102

Cited by 115 publications

(50 citation statements)

References 30 publications

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“…This opsonic antibody is initially secretory IgA but is soon superseded by more effective IgG antibody (29). Much of the IgG antibody is probably produced by plasmacytes in regional lymph nodes and amves in the bronchial lumen via transudation from serum which is enhanced by inflammation (30).…”

Section: Discussionmentioning

confidence: 99%

Altered Antibody Isotype in Cystic Fibrosis. Possible Role in Opsonic Deficiency

et al. 1986

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ABSTRACT'. Patients with cystic fibrosis (CF) whose respiratory tracts are colonized with Pseudomonas aeruginosa (PA) may develop a specific opsonic deficiency for alveolar macrophage phagocytosis of PA. We examined the possible role of altered antibody (Ab) isotype in this phenomenom by measuring serum levels and distribution of IgG and IgG subclass Ab (IgGl, IgG2, IgG3, and IgG4) to the major opsonic immunodeterminant, serotype-specific lipopolysaccharide (LPS), by means of enzyme-linked immunosorbent assays employing monoclonal secondary antibodies, and comparing these results to the serum opsonic capacity in an in vitro murine alveolar macrophage phagocytic assay. Twenty-one patients with CF who were colonized with PA had approximately a 30-fold elevation of PA LPS IgG Ab levels and higher IgG subclass 1-4 Ab compared to 10 uncolonized patients with CF and 11 healthy controls (p < 0.05-0.0005 depending on the isotype). Colonized patients with CF had a shift in PA LPS Ab distribution toward IgG3 compared to uncolonized patients with CF (p < 0.02). A surprising finding was that uncolonized patients with CF had lower levels (p < 0.05) and proportion (p < 0.002) of PA LPS IgG2 Ab than controls, with an apparent shift to higher levels and proportion of PA LPS IgG4 (p < 0.01). Serum from colonized patients with CF showed diminished opsonic capacity for phagocytosis of PA compared to uncolonized patients and controls (p < 0.005), with 42% showing inhibitory activity.

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Section: Discussionmentioning

confidence: 99%

Altered Antibody Isotype in Cystic Fibrosis. Possible Role in Opsonic Deficiency

et al. 1986

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“…With this prophylactic regimen, epithelial, endothelial, and pleural injury were prevented, and there was a significant decrease in the number of bacteria recovered from the lung. (3)(4)(5). These studies have also suggested that the most protective antibodies against P. aeruginosa are opsonic rather than bactericidal, thus providing a rationale for P. aeruginosa immunization strategies that emphasize augmentation of humoral rather than cellmediated immunity (3).…”

Section: Abstract Introductionmentioning

confidence: 99%

“…aeruginosa pneumonia remains between 50 and 80% (2), establishing the need for new treatment modalities or improved prophylactic measures. Earlier studies have established that serotype-specific humoral immunity results in a significant augmented host defense against blood-borne P. aeruginosa (3)(4)(5). These studies have also suggested that the most protective antibodies against P. aeruginosa are opsonic rather than bactericidal, thus providing a rationale for P. aeruginosa immunization strategies that emphasize augmentation of humoral rather than cellmediated immunity (3).…”

Section: Introductionmentioning

confidence: 99%

Pseudomonas aeruginosa-induced lung and pleural injury in sheep. Differential protective effect of circulating versus alveolar immunoglobulin G antibody.

Pittet¹,

Matthay²,

Pier³

et al. 1993

J. Clin. Invest.

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IntroductionThe overall objective of these studies was to determine whether IgG antibody to Pseudomonas aeruginosa would modify the acute lung and pleural injury that developed over 24 h after the instillation of 1010 live P. aeruginosa into the distal airspaces of one lung in unanesthetized sheep. Using a quantitative experimental model to measure protein permeability across the alveolar epithelial, lung endothelial, and pleural mesothelial barriers, the effect of IgG antibody to P. aeruginosa was examined under four different experimental conditions. First, the effect of IgG antibody to P. aeruginosa in the circulation was examined by instilling 1010 live P. aeruginosa in 5% ovine albumin in sheep that had been vaccinated. Under these conditions, the presence of circulating IgG antibody to P. aeruginosa reduced lung endothelial injury but did not modify the lung epithelial or pleural injury caused by intraalveolar P. aeruginosa. Therefore, the second experimental protocol determined the effect of instilling immune serum from a sheep that had been vaccinated so that IgG antibody to P. aeruginosa was present in both the circulation and in the airspaces along with instillation of live bacteria. Under these conditions, injury to the lung endothelium, alveolar epithelium, and pleural space was completely prevented. Therefore, the third protocol examined the protective effect of instillation of IgG antibody to P. aeruginosa in the airspaces concurrent with the live bacteria. Interestingly, intraalveolar IgG antibody to P. aeruginosa prevented all evidence of lung epithelial and pleural injury, and this effect was associated with a marked decrease in the number of viable bacteria in the lung after 24 h. Therefore, the fourth protocol examined the prophylactic effect of instillation of the specific IgG antibody to P. aeruginosa 24 h before instillation of the bacteria. With this prophylactic regimen, epithelial, endothelial, and pleural injury were prevented, and there was a significant decrease in the number of bacteria recovered from the lung. (3)(4)(5). These studies have also suggested that the most protective antibodies against P. aeruginosa are opsonic rather than bactericidal, thus providing a rationale for P. aeruginosa immunization strategies that emphasize augmentation of humoral rather than cellmediated immunity (3). In contrast to older vaccines, which contained the whole endotoxin antigen, a Pseudomonas vaccine containing a high molecular weight, immunogenic 0-specific polysaccharide antigen, but lacking the toxic lipid A component, has been shown to be well tolerated and immunogenic in normal human volunteers (6). This vaccine also has been shown to achieve a plasma level of IgG antibody to P. aeruginosa comparable to the levels measured in patients who survived P. aeruginosa sepsis (7,8). Also, immunization with P. aeruginosa 0-specific polysaccharide antigen has improved survival after a homologous bacterial challenge in both burned and granulocytopenic mice and in a model of pneumonia in gui...

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“…This is an important part of efficient lung host defense. Although much is known about the phagocytic ability of AM (3)(4)(5)(6), and the armamentarium of enzymes and secretory products they possess (7), less is known about the interrelation of stimulated or "challenged" macrophages with other arms of the inflammatory response (8). Recent evidence suggests that through the elaboration of chemo-tactic factors, AM have the capability of attracting secondary phagocytic cells such as polymorphonuclear granulocytes (PMN).…”

Section: Introductionmentioning

confidence: 99%

Alveolar macrophage-derived chemotactic factor: kinetics of in vitro production and partial characterization.

et al. 1980

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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.

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Specificity of opsonic antibodies to enhance phagocytosis of Pseudomonas aeruginosa by human alveolar macrophages.

Cited by 115 publications

References 30 publications

Altered Antibody Isotype in Cystic Fibrosis. Possible Role in Opsonic Deficiency

Altered Antibody Isotype in Cystic Fibrosis. Possible Role in Opsonic Deficiency

Pseudomonas aeruginosa-induced lung and pleural injury in sheep. Differential protective effect of circulating versus alveolar immunoglobulin G antibody.

Alveolar macrophage-derived chemotactic factor: kinetics of in vitro production and partial characterization.

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