[Study on pathogenetic role of myeloperoxidase, tumor necrosis factor alpha, interferon gamma in chronic airway infection with Pseudomonas aeruginosa].
This study was performed to demonstrate the pathogenetic role of mucoid-alginate produced by Pseudomonas aeruginosa in relation to immuno-interaction in host cells. The obtained results are as follows. 1. Clinical Observation The concentration of MPO, TNF alpha, and IFN gamma in peripheral blood of 37 cases of chronic airway infection were observed. The cases were divided into the groups with mucoid strain positive (21 cases) and negative (16 cases), and each group was also divided into subgroups with active clinical symptom and without. High concentration of serum IFN gamma was shown in the group of mucoid strain positive cases (0.10 +/- 0.08 IU/ml in healthy volunteers group, 0.54 +/- 0.56 IU/ml in mucoid group with symptom: p < 0.01, 0.09 +/- 0.15 IU/ml in mucoid group without symptom, 0.13 +/- 0.13 IU/ml in non-mucoid group with symptom, 0.09 +/- 0.13 IU/ml in non-mucoid group without symptom). But plasma concentrations of MPO and serum concentrations of TNF alpha were not increased in all groups, except MPO in non-mucoid group with symptom. It indicates that IFN gamma has a characteristic role in chronic airway infection with mucoid Pseudomonas aeruginosa (P. aeruginosa). 2. Experimental Observation One hundred twenty-two of alginate-immunized mice were made by 5 times of intraabdominal injection with purified alginate extracted from mucoid P. aeruginosa PT-1252. 4 x 10(6) CFU/body of mucoid P. aeruginosa PT-1252 or 20 micrograms/body of purified alginate was intubated per trachea into the immunized mice, and changes in mean fluorescence intensity (MFI) of MPO and TNF alpha on neutrophils and IFN gamma on CD3 positive lymphocytes in BALF were observed. MFI of MPO (99.7 +/- 16.5-->177.0 +/- 23.1: p < 0.001) and TNF alpha (59.2 +/- 13.3-->197.0 +/- 62.0: p < 0.001) were increased on day 2 and they were kept up till on day 30 in P. aeruginosa group. But in alginate group they were temporally decreased on day 2, and they were gradually increased (MPO: 99.7 +/- 16.5-->212.6 +/- 12.1: p < 0.001, TNF alpha: 59.2 +/- 13.3-->162.4 +/- 30.9: p < 0.01). The temporally decrease of MPO and TNF alpha on day 2 in alginate group may suggest that a large amount of alginate inhibits neutrophils chemotaxis. MFI of IFN gamma in P. aeruginosa was also increased (110.0 +/- 32.9-->198.3 +/- 23.0: p < 0.01) on day 2 and it was gradually decreased on day 30 (156.0 +/- 13.8). In alginate group, MFI of IFN gamma in BALF was increased on day 5 (110.0 +/- 32.9-->201.0 +/- 49.3: p < 0.001) and kept a high level till day 30 (223.0 +/- 57.5: p < 0.01). In morphological, the moderate grade of lymphocytes infiltration observed in intersitial area of lung tissue on both groups of P. aeruginosa and alginate intubation mice. The findings was continuously seen from day 5 through day 30. The lymphocytes infiltration appeared in lung tissue can be though as an result of immuno-interaction with IFN gamma positive lymphocytes and mucoid-alginate. Inferences are drawn from the clinical results and the experimental ones that the CD3 positive IFN gamma lymphocytes expressed by immunological interaction with mucoid-alginate and the IFN gamma lymphocytes (Th1 like cells) plays an important role on advancement of chronic airway infection with mucoid P. aeruginosa.
Takeda
H
H
First Department of Internal Medicine, Kyorin University, School of Medicine.
D000464:Alginates / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D005260:Female; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D009195:Peroxidase / Q000502:physiology*; D011552:Pseudomonas Infections / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000464:Alginates; D006603:Hexuronic Acids; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D020723:Glucuronic Acid; D009195:Peroxidase