Ena Ray Banerjee
Background: Inflammation and degeneration are the two edged swords that impale a pulmonary system with the maladies like asthma and idiopathic pulmonary fibrosis. To explore critical role players that orchestrate the etiology and pathogenesis of these diseases, we used various lung disease models in mice in specific genetic knockout templates. Materials and methods: Acute and chronic allergic asthma and idiopathic pulmonary fibrosis models in mouse were developed in various genetic knockout templates, namely α4Δ/ Δ (α41-/-), β2-/-, and α4-/- β2 mice, and the following parameters were measured to assess development of composite asthma phenotype- (i) airway hyper responsiveness to methacholine by measuring lung resistance and compliance by invasive, and Penh by non-invasive, plethysmography (ii) in situ inflammation status in lung parenchyma and lung interstitium and also resultant airway remodelling measured by histochemical staining, namely Masson’s Trichrome staining and Hematoxylin & Eosin staining, (iii) formation of metaplastic goblet cells around lung airways by Alcian blue staining, (iv) measurement of Th1 and Th2 cytokines in serum and bronchoalveolar lavage fluid (BALf), (v) serum allergen-specific IgE. Specifically, ovalbumin-induced acute allergic asthma model in mice was generated in WT (wild type) and KO (knockout) models and readouts of the composite asthma phenotype viz. airway hypersensitivity, serum OVA-specific IgE and IgG, Th2 cytokine in BALf and lymphocyte cell subsets viz. T, B cells, monocytes, macrophages, basophils, mast cells and eosinophils (by FACS and morphometry in H&E stained cell smears) were assessed in addition to lung and lymph node histology. Results: We noticed a pattern of cellular traffic between bone marrow (BM)→ peripheral blood (PB) → lung parenchyma (LP) → (BALf) in terms of cellular recruitment of key cell sub-types critical for onset and development of the diseases which is different for maintenance and exacerbations in chronic cyclically occurring asthma that leads to airway re-modelling. While inflammation is the central theme of this particular disease, degeneration and shift in cellular profile, subtly modifying the clinical nature of the disease were also noted. In addition we recorded the pattern of cell movement between the secondary lymphoid organs namely, the cervical, axillary, ingunal, and mesenteric lymph nodes vis-à-vis spleen and their sites of poiesis BM, PB and lung tissue. While mechanistic role is the chief domain of the integrins (α4 present in the integrin VLA-4 or α4β1 a component of VCAM-1 as well as β2 which the CD-18 or ICAM-1 are comprised of). Concluding remarks: The present paper thoroughly compares and formulates the pattern of cellular traffic among the three nodes of information throughput in allergic asthma immunobiology, namely, primary lymphoid organs (PLO), secondary lymphoid organs (SLO), and tissue spaces and cells where inflammation and degeneration is occurring within the purview of the disease pathophysiological onset. Ancillary signals in the above models and reports some interesting findings with respect to adult lung stem cell niches and its resident progenitors and their role in pathogenesis and disease amelioration.
