Lymphocytes Migrate from the Blood into the Bronchoalveolar Lavage and Lung Parenchyma in the Asthma Model of the Brown Norway Rat

Abstract

Lymphocyte migration from the blood into the lung has been suggested as being responsible for the increase of lymphocytes, in particular CD4 T cells, in the bronchoalveolar lavage (BAL) and bronchial mucosa in human asthma, but so far there has been no direct proof. We studied lymphocyte immigration and lymphocyte subpopulations in three lung compartments in ovalbumin (OVA)-sensitized and -challenged brown Norway (BN) rats. Increased numbers of CD4 and interleukin 2 (IL-2) receptor-positive T cells were found in the BAL and lung parenchyma in treated animals, but also increased numbers of CD8 T cells, B cells, and natural killer (NK) cells. For direct proof of lymphocyte migration from the blood into the lung, leukocytes were labeled with a fluorescent dye, 5- (and 6-) carboxyfluorescein-diacetate-succinimidyl-ester (CFSE), and injected intravenously immediately prior to OVA aerosol challenge. One day after challenge the number of CFSE(+), i.e., newly immigrated lymphocytes, was determined by flow cytometry gated on the lymphocyte cluster. A 15 times (1.5 times) higher number of CFSE(+) lymphocytes was found in the BAL (the lung parenchyma) of treated animals in comparison with control rats. In the BAL 51.8% of CFSE(+) cells were CD4-positive (parenchyma 72.7%) and 29.4% IL-2 receptor-positive (parenchyma 34.2%). There was no difference whether the leukocytes for labeling and injection were obtained from untreated or from OVA-sensitized donor animals. Our data show that lymphocyte immigration is at least in part responsible for the increase in lymphocyte numbers in the BAL and lung parenchyma in this animal asthma model.

The effect of brevenal on brevetoxin-induced DNA damage in human lymphocytes

“…Asthma is a hypersensitivity to an allergen or foreign substance that can trigger the immune response (Schuster et al 2000). In addition to being neurotoxic and gastrointestinally toxic, brevetoxins cause airway irritation, airway constriction, and bronchoconstriction (Backer et al 2003).…”

Lymphocytes in the bronchoalveolar space reenter the lung tissue by means of the alveolar epithelium, migrate to regional lymph nodes, and subsequently rejoin the systemic immune system

“…The fate and function of these bronchoalveolar lymphocytes are not well understood. Immigration of lymphocytes from blood into the bronchoalveolar space has been shown but seems to be slow in healthy rats with an increase during inflammation (Schuster et al, 2000). In addition, only 0.5-1% of the bronchoalveolar lymphocytes proliferate locally so that bronchoalveolar lymphocytes seem to form a stable cell population (Kracke et al, 2000).…”

“…In vitro labeled cells had to be used, because the immunohistological detection of the congenic RT7 b cells in plastic-embedded sections produced inconstant results. For labeling, the donor cells were incubated with FITC (Willfü hr et al, 1989) for 15 min at 37°C in RPMI 1640 at a final concentration of 50 g FITC/ml and 2% fetal calf serum or with CFSE for 30 min at 37°C (Schuster et al, 2000). The lungs of the other three animals were investigated by confocal laser scanning microscopy (CLSM) so that unlabeled RT7 b cells could be used.…”

“…The dynamics of these bronchoalveolar lymphocytes are dependent on their entry, proliferation, apoptosis, and exit from this pool . The immigration of lymphocytes into the bronchoalveolar space has been shown in animals, e.g., by chimerism after lung transplantation Schuster et al, 2000). The bronchoalveolar space, however, seems not to be the graveyard for these cells.…”

NK cells in immunotolerant organs

“…Therefore, a fast response of innate immune cells is required, and concurrently, this local immune response must be regulated by specialized immune regulatory mechanisms to protect the host from selfattacks and ensure normal physical functions. Only a few hours after the occurence of inflammation in the lungs, large numbers of NK cells are recruited to the lungs and become activated as cytokine-secreting cells, primarily secreting IFN-c. 116,117 When inflammation occurs, alveolar macrophages rapidly produce inhibitory cytokines such as IL-10 and TGF-b to inhibit inflammation, 118 thus inhibiting the cytotoxic functions of pulmonary NK cells, even though the NK cells remain able to bind to the target cells. 119,120 The functional abilities of pulmonary NK cells are restored upon stimulation with type I interferon.…”