Immunoglobulin and ?2-microglobulin concentrations in bronchoalveolar lavage of children and adults

Ratjen, Félix; Kreuzfelder, E.

doi:10.1007/bf00164635

Cited by 6 publications

(6 citation statements)

References 21 publications

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“…This variability applies to multiple samples taken from the same patient as well as samples obtained from different patients. A number of attempts have been made to normalize BAL samples based on various denominators, including secretory IgA and urea (31)(32)(33). Despite these attempts, an appropriate denominator has not as yet been widely agreed upon.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Kwong

Jones

Cayabyab

et al. 1998

Journal of Clinical Immunology

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Mechanisms that regulate cytokine-mediated inflammation in the lungs of preterm infants, including factors which regulate production of the chemokine IL-8, remain poorly defined. Sequential bronchoalveolar lavage samples were obtained from preterm newborns with hyaline membrane disease over a 28-day period. Bronchoalveolar lavage cell cytokine relationships were evaluated and the differential regulation of IL-8 by IL-1beta and TNFalpha was studied in a short-term culture system. In vivo, IL-8 and IL-1beta protein levels correlated closely with each other and with macrophage counts. In cell culture, exogenous anti-IL-1beta antibody led to a 40% maximum inhibition (approximately) of IL-8 production by lipopolysaccharide stimulated lung inflammatory cells. Comparable amounts of exogenous anti-TNFalpha antibodies achieved a 15% maximum inhibition (approximately) of IL-8 production. Anti-IL-1beta and anti-TNFalpha antibodies in combination did not inhibit IL-8 production beyond that achieved by anti-IL-1beta antibody alone. These results, in preterm newborns, support the concept of lung inflammation mediated in part by a macrophage, IL-1beta, and IL-8 cell cytokine pathway. The results also suggest that factors other than IL-1beta and TNFalpha regulate IL-8 expression in the lungs of preterm infants.

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Section: Discussionmentioning

confidence: 99%

Untitled

Kwong

Jones

Cayabyab

et al. 1998

Journal of Clinical Immunology

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“…B2M is essential for antigen binding and known to play a role in maintaining the correct structure of the MHC class I complex [ 42 ]. In BAL fluid of healthy adults, it reaches concentrations of 0.08 mg/l with higher concentrations observed in children [ 43 ], while serum concentrations of B2M range between 1 and 3 mg/l [ 20 ]. A large fragment of B2M has also been detected in the culture supernatant of respiratory epithelial cells upon stimulation with IL-1ß [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Respiratory ß-2-Microglobulin exerts pH dependent antimicrobial activity

et al. 2020

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The respiratory tract is a major entry site for microbial pathogens. To combat bacterial infections, the immune system has various defense mechanisms at its disposal, including antimicrobial peptides (AMPs). To search for novel AMPs from the respiratory tract, a peptide library from human broncho-alveolar-lavage (BAL) fluid was screened for antimicrobial activity by radial diffusion assays allowing the efficient detection of antibacterial activity within a small sample size. After repeated testing-cycles and subsequent purification, we identified ß-2-microglobulin (B2M) in antibacterially active fractions. B2M belongs to the MHC-1 receptor complex present at the surface of nucleated cells. It is known to inhibit the growth of Listeria monocytogenes and Escherichia coli and to facilitate phagocytosis of Staphylococcus aureus . Using commercially available B2M we confirmed a dose-dependent inhibition of Pseudomonas aeruginosa and L. monocytogenes . To characterize AMP activity within the B2M sequence, peptide fragments of the molecule were tested for antimicrobial activity. Activity could be localized to the C-terminal part of B2M. Investigating pH dependency of the antimicrobial activity of B2M demonstrated an increased activity at pH values of 5.5 and below, a hallmark of infection and inflammation. Sytox green uptake into bacterial cells following the exposure to B2M was determined and revealed a pH-dependent loss of bacterial membrane integrity. TEM analysis showed areas of disrupted bacterial membranes in L. monocytogenes incubated with B2M and high amounts of lysed bacterial cells. In conclusion, B2M as part of a ubiquitous cell surface complex may represent a potent antimicrobial agent by interfering with bacterial membrane integrity.

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“…Our data are more in line with the majority of adult studies and a recent study performed in healthy children and adults. [23][24][25] We addressed the question of whether there is a specific role for one of the IgG-subclasses in the immunological defense of the respiratory tract, as has been proposed for IgG-4 in the study of Merrill et al 10 For this purpose, IgG-subclass distribution was measured in serum and compared to BALF. In healthy children and patients with chronic chest infection we found good correlations between relative serum concentrations of IgGsubclasses and the corresponding lavage concentrations.…”

Section: Discussionmentioning

confidence: 99%