Lung interstitium

Pulmonary fibrosis is the medical term given to an end-stage restrictive lung disorder characterized by excessive deposition of connective tissue (predominantly collagen) in the lung interstitium. This deposition is caused by some type of acute or subacute injury to the lung that triggers inflam-... 

Even in healthy lungs, collagen is the most abundant component of the lung interstitium (elastin and proteoglycan being the other primary compo-... 

Edema Caused by Lymphatic Dysfunction. Pulmonary lymphatic insufficiency resulting from lymphatic carcinoma, silicosis, anesthesia, or sedative drug overdose can cause a decreased clearance of fluid from the lung via the lymphatics. Because of the absence of this important mechanism for fluid removal from the lung, lymphatic insufiiciency can rapidly lead to an accumulation of fluid in the lung interstitium and ultimately to pulmonary edema. 

Probably due to the narrow interstitium of the lung, lymphocytes had been overlooked in this area for a long time. In the rabbit, Schwarz (1963) described oval to spindle-shaped lymphoid cells with plumpy projections. Holt et al. (1986) carefully isolated, quantified and characterised lymphocytes in the interstitium of the human lung. For the whole lung interstitium a total of about 10 lymphocytes were calculated, which is equivalent to the lymphocyte number in the circulating blood pool in humans. In the interstitium of the human lung natural killer cells (NK cells) have also been identified (Weissler et al. 1987). The lymphocytes in the interstitial pool of the rat revealed a subset composition different from that in the peripheral blood (Fliegert et al. 1995). 

Actin, the contractile protein within cells, maybe responsible for movement of asbestos particles through the epithelium to the lung interstitium where the fibres react with macrophages and fibroblasts (Brody et al. 1983). 

As noted above, LIP is part of a spectrum of pulmonary lymphoid proliferations, ranging from follicular bronchitis-bronchiolitis to low-grade malignant lymphoma, patterns which may be difficult to distinguish from each other (5). When reactive lymphoid nodules are centered in a lymphatic distribution about airways, vessels, and interlobular septa, the disease is termed follicular bronchitis/ bronchiolitis [or pulmonary lymphoid hyperplasia (PLH)] in the pediatric AIDS literature) (60). As the disease becomes more florid and the reactive lymphoid infiltrate extends into the lung interstitium, then the process is termed LIP (3). 

Wells AU, Lorimer S, Majumdar S, et al. Fibrosing alveolitis in systemic sclerosis increase in memory T-cells in lung interstitium. Eur Respir J 1995 8 266-271. Luzina IG, Atamas SP, Wise R, et al. Gene expression in bronchoalveolar lavage cells from scleroderma patients. Am J Respir Cell Mol Biol 2002 26 549-557. Bolster MB, Ludwicka A, Sutherland SE, et al. Cytokine concentrations in bronchoalveolar lavage fluid of patients with systemic sclerosis. Arthritis Rheum 1997 40 743-751. 

In vitro and in vivo studies suggested that aerosolizing E25 would deliver the therapeutic primarily to the ELE with low and limited delivery to the serum. The quantity delivered to lung interstitium could not be determined. To evaluate the potential efficacy of topical delivery to the lung surface and to estimate dose, a suitable animal model would be advantageous. However, no suitable animal model was available. Rodent models of asthma could not be used to evaluate efficacy since E25 does not bind to rodent IgE. Also, although E25 does bind to monkey IgE, at the time of these studies there was no well-characterized monkey model of asthma. We decided that the fastest way to evaluate the efficacy of aerosolized E25 was to use a human bronchoprovocation model of asthma since systemic delivery of E25 was found to be efficacious in this model (21,22). 

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