Experimental murine hypersensitivity pneumonitis

doi:10.1016/0008-8749(91)90354-E

Cellular Immunology

Volume 136, Issue 2, September 1991, Pages 303-317

https://doi.org/10.1016/0008-8749(91)90354-E Get rights and content

Abstract

To establish a model of experimental hypersensitivity pneumonitis (EHP) in mice and to examine the influence of genetic background on the pulmonary inflammatory response to Micropolyspora faeni, we determined the responses of C57BL/6, SJL/J, and C3H/HeJ mice to intratracheal (i.t.) injections of M. faeni. Recipient animals received lymph node cells (LNC), peritoneal exudate cells (PEC), and spleen cells (SC) from sensitized mice cultured in vivo with M. faeni. Controls included serum containing anti-M. faeni antibody; uncultured SC from M. faeni-sensitized donors, and M. faeni-cultured SC from ovalbumin (OA)-sensitized donors. Recipients were challenged i.t. with M. faeni or normal saline 48 hr after the cell or serum transfer. We developed a model of EHP in mice. Increasing amounts of i.t. M. faeni were associated with increasing extent of pulmonary inflammation with no difference between the mouse strains. There was substantial increase of the extent of pulmonary abnormalities in the animals receiving cultured SC. The number of transferred cells and the M. faeni concentration correlated with the extent of pulmonary histologic abnormalities. Cultured PEC and LNC could transfer EHP in C3H/HeJ mice only. Serum containing anti-M. faeni antibody, cultured SC from OA-sensitized donors, and noncultured SC from sensitized donors could not transfer EHP. We conclude that it is possible to adoptively transfer EHP.

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Where asthma and hypersensitivity pneumonitis meet and differ: Noneosinophilic severe asthma
2009, American Journal of Pathology
Citation Excerpt :
As a real-life HP-eliciting antigen, S. rectivergula possesses endogenous immunogenic characteristics, and HP can be established in mice by repeated intranasal instillation without adjuvant support.58,59 However, most mouse protocols to induce HP rely on a systemic sensitization against S. rectivergula in the presence of complete Freund's adjuvant (CFA) as the immunogenic co-factor, followed by intratracheal administration of S. rectivergula,60 thus leading to a HP-like neutrophilic, Th1-driven pulmonary inflammation. Interestingly, systemic sensitization to OA, the prototypical allergen used in mouse asthma models, using CFA (instead of alum as in experimental asthma induction), followed by inhalational OA challenge also induced Th1-driven responses with neutrophilic airway inflammation in the perivascular and peribronchiolar areas and little to no airway hyperreactivity or mucus production.61
Asthma is a type-I allergic airway disease characterized by Th₂ cells and IgE. Episodes of bronchial inflammation, eosinophilic in nature and promoting bronchoconstriction, may become chronic and lead to persistent respiratory symptoms and irreversible structural airway changes. Representative mostly of mild to moderate asthma, this clinical definition fails to account for the atypical and often more severe phenotype found in a considerable proportion of asthmatics who have increased neutrophil cell counts in the airways as a distinguishing trait. Neutrophilic inflammation is a hallmark of another type of allergic airway pathology, hypersensitivity pneumonitis. Considered as an immune counterpart of asthma, hypersensitivity pneumonitis is a prototypical type-III allergic inflammatory reaction involving the alveoli and lung interstitium, steered by Th₁ cells and IgG and, in its chronic form, accompanied by fibrosis. Although pathologically very different and commonly approached as separate disorders, as discussed in this review, clinical studies as well as data from animal models reveal undeniable parallels between both airway diseases. Danger signaling elicited by the allergenic agent or by accompanying microbial patterns emerges as critical in enabling immune sensitization and in determining the type of sensitization and ensuing allergic disease. On this basis, we propose that asthma allergens cause severe noneosinophilic asthma because of sensitization in the presence of hypersensitivity pneumonitis-promoting danger signaling.
Experimental hypersensitivity pneumonitis: Role of MCP-1
2003, Journal of Laboratory and Clinical Medicine
Inhalation of Saccharopolyspora rectivirgula causes “farmer's lung” disease, a classic example of hypersensitivity pneumonitis (HP). Monocyte chemoattractant protein-1 (MCP-1) is increased in the bronchoalveolar lavage fluid of mice challenged with S rectivirgula, and S rectivirgula induces MCP-1 secretion by alveolar macrophages. We tested the hypothesis that MCP-1 and its receptor CC chemokine receptor-2 (CCR2) are essential to the development of experimental HP by treating mice with MCP-1 antibody and using CCR2^−/− mice. Administration of anti–MCP-1 did not change the response to intratracheally administered S rectivirgula. CCR2^−/− animals responded in a fashion similar to that of wild-type animals to intratracheally administered.S rectivirgula. To determine the influence of the MCP-1–CCR2 interaction in vitro, we transferred S rectivirgula–cultured spleen cells from S rectivirgula–sensitized mice, to naïve recipients. Later, challenge of the recipients with intratracheal S rectivirgula and examination of both lung histology and bronchoalveolar lavage fluid characteristics were used to determine whether adoptive transfer had occurred. We found that cultured cells from CCR2^−/− animals were fully capable of adoptive transfer. We conclude that interaction of MCP-1 with CCR2 is not necessary for the development of pulmonary inflammation in response to intratracheally administered S rectivirgula or cells able to adoptively transfer experimental HP.
Mediators of hypersensitivity pneumonitis
2000, Journal of Laboratory and Clinical Medicine
Citation Excerpt :
Male C57Bl/6 and BALB/cAnCr mice (NCI, Frederick Cancer Research Facility, Frederick, MD) were housed in laminar flow hoods with high-efficiency particulate filtered air in the Veterinary Medical Unit at the Albuquerque VA Medical Center, which is fully accredited by the American Association for laboratory animal care. S rectivirgula was obtained from V. Kurup, Medical School of Wisconsin, Milwaukee, WI, and prepared as previously described.5,6 We prepared a soluble extract of the S. rectivirgula that was tested for endotoxin content with a modified Limulus assay (BioWhittaker, Walkersville, MD).
Inhalation of Saccharopolyspora rectivirgula (S. rectivirgula ) causes farmer's lung disease, a classic example of hypersensitivity pneumonitis (HP). HP is characterized by bronchoalveolar lavage fluid (BALF) neutrophilia (within the first 48 hours after inhalation), followed by BALF lymphocytosis. We utilized a well-described murine model of HP to determine the timing of the appearance of the C-C chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α); the inflammatory cytokines tumor necrosis factor (TNF), interleukin-1α (IL-1α), and interleukin-6 (IL-6); and the Th1-differentiating cytokine interleukin-12 (IL-12) in BALF. After a single intratracheal administration of S. rectivirgula , there was remarkable BALF neutrophilia (peak 24 to 48 hours), followed by a BALF lymphocytosis (peak 48 to 72 hours) in both C57Bl/6 and BALB/c mice that was preceded by the appearance of MIP-1α in BALF (peak 4 to 6 hours) and MCP-1 (peak at 48 hours). In both strains of mice there was a striking increase of BALF IL-12 (peak 48 to 72 hours). There was also an increase in BALF IL-6, IL-1α, and TNF that was greater in the BALB/c mice than in the C57Bl/6 mice. S. rectivirgula induced the secretion of MIP-1α, MCP-1, IL-6, IL-1α, and IL-12 from the murine macrophage cell line J774A.1; MIP-1α, IL-6, IL-1α, IL-12, and TNF from C57Bl/6 alveolar macrophages; and IL-1α, IL-6, and TNF—but not IL-12—from BALB/c alveolar macrophages. We conclude that chemokines and cytokines induced by intratracheal administration of S. rectivirgula precede BALF neutrophilia and lymphocytosis and may cause differentiation of Th1 cells; we also conclude that pulmonary macrophages represent a potential source of these substances. (J Lab Clin Med 2000;136:29-38)
Th1 CD4<sup>+</sup> cells adoptively transfer experimental hypersensitivity pneumonitis
1997, Cellular Immunology
Cultured cells fromMicropolyspora faeni-sensitized donors can adoptively transfer murine experimental hypersensitivity pneumonitis (EHP). To determine whether the CD4⁺cells responsible for transfer have characteristics of Th1 or Th2 cells, we established cell lines from lung-associated lymph nodes ofM. faeni-sensitized C3H/HeJ mice by culturing with antigen and either IFN-γ, IL2, and anti-IL4, or IL4. Cell lines were stimulated regularly with antigen, fresh antigen-presenting cells, and the cytokine/anti-cytokine antibody cocktail. At various times after initiation of culture, cells were injected intravenously into recipients, which were then challenged intratracheally withM. faeniand sacrificed and the extent of pulmonary inflammatory response was determined. IFN-γ, IL4, and IL10 levels were determined in supernatants of cell cultures stimulated withM. faenito characterize the cell lines as Th1 (IFN-γ, but low IL4 and IL10 secretion) or Th2 (IL4 and IL10, but low IFN-γ secretion). Cell lines were differentiated into either Th1 (IFN-γ = 310 ± 45 U/ml, IL4 = 0.10 ± 0.1 U/ml, IL10 = 1750 ± 75 pg/ml, >99% CD4⁺) cell lines by Day 16 of culture or Th2 cell lines (IFN-γ = 1.8 ± 1.0 U/ml, IL4 = 830 ± 388 U/ml, IL10 = 51,700 ± 10,900 pg/ml, >96% CD4⁺) by Day 30. Th1 cell lines were able to adoptively transfer EHP whereas Th2 cell lines were unable to adoptively transfer EHP. The ability to transfer EHP was directly related to the amount of IFN-γ and inversely to the amount of IL4 secreted by antigen-stimulated cells. We conclude that it is possible to produce CD4⁺cell lines with either Th1 or Th2 characteristics from lung-associated lymph nodes of mice exposed toM. faeniand that only Th1 CD4⁺cell lines can adoptively transfer EHP.
Hypersensitivity pneumonitis in a patient with hypogammaglobulinemia
1996, Journal of Allergy and Clinical Immunology
Co-modulation of T cells and B cells enhances the inhibition of inflammation in experimental hypersensitivity pneumonitis
2022, Respiratory Research

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^☆: This work was supported by the Veterans Administration Research Service and University of New Mexico RAC Grant R8116.

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Experimental murine hypersensitivity pneumonitis☆

Abstract

J. Allergy Clin. Immun

Exp. Pathol

J. Allergy Clin. Immunol

Cell. Immunol

J. Immunol. Methods

Adv. Immunol

Cell. Immunol

Chest

J. Allergy Clin. Immunol

Semin. Respir. Med

Am. Rev. Respir. Dis

Am. Rev. Respir. Dis

Am. Rev. Respir. Dis

Int. Arch. Allergy Appl. Immunol

J. Immunol

Int. Arch. Allergy Appl. Immunol

Int. Arch. Allergy Appl. Immunol

J. Pathol

Acta Pathol. Microbiol. Immunol. Scand. A

J. Exp. Pathol

Am. Rev. Respir. Dis

Science

Eur. J. Immunol

J. Immunol

Science

Clin. Exp. Immunol

J. Immunol