Extensive Inflammatory Cell Infiltration Research Articles

An Experimentally Induced Fat Embolism in the Rabbit Lung: High-resolution CT and Pathologic Findings

Purpose: To assess the high-resolution CT and pathologic findings of fat embolism experimentally induced in rabbit lung. Materials and Methods: Twelve rabbits were divided into four groups, namely control, 2-hour, 24-hour, and 72-hour, with three rabbits in each, and closed tibiofibular fractures were induced. After the rabbits were sacrificed, high-resolution CT scanning of the artificially inflated lungs was performed, and the CT findings were analyzed by two radiologists. They determined the presence or absence of ground glass opacity or consolidation, the extent of the lesions (using a 10% grading scale), and their distribution, reaching a consensus. The pathologic findings were analyzed using the specimens prepared by H & E and Oil-red O staining. Results: Although the high-resolution CT findings of pulmonary fat embolism were nonspecific, bilateral patchy ground glass opacity (100%), and focal air-space consolidation surrounding the bronchovascular bundle (89%) were most common. In all groups, the occlusion of vessels by fat globules was confirmed by Oil-red Ostaining. The microscopic findings included focal pulmonary hemorrhage, edema, alveolar collapse, and extensive infiltration of inflammatory cells in the lung parenchyma. The 24-hour group showed more extensive change in high-resolution CT and pathologic findings than did the others. Conclusion: Fat embolism in rabbit lung may occur after closed tibio-fibular fracture. The extent of the lesion revealed by high-resolution CT correlated closely with the pathologic findings. High-resolution CT may thus be helpful for the detection of pulmonary fat embolism and evaluation of its extent.

Induction of experimental autoimmune neuritis in CD4 −8 − C57BL/6J mice

The C57BL/6J mice strain is known to be reputedly resistant to induction of experimental autoimmune neuritis (EAN), an animal model of Guillain–Barré syndrome in humans. Here we describe the induction of EAN in mice of the C57BL/6J background by transfer into naive syngeneic recipients bovine peripheral nerve myelin (BPM)-primed donor lymph node cells that had been stimulated in vitro with the bovine peripheral nervous system (PNS) myelin P2 protein peptide 57–81 followed by challenge with BPM, Freund's complete adjuvant and pertussis toxin. EAN was more severe, both clinically and histologically, and accompanied by extensive infiltration of inflammatory cells and demyelination in peripheral nerves when examined on day 30 after transfer of primed T cells from CD4 −8 − mice into identical naive hosts than after transfer of cells from primed wild type, CD4 −/ − or CD8 −/ − mice to corresponding recipient animals. EAN in CD4 −8 − mice was also associated with elevated numbers of P2 peptide-reactive interferon-γ (IFN-γ) secreting cells and αβ T cells were present in lymph nodes and spleens. The data suggest that PNS myelin activated T cells from an EAN-resistant mice strain are capable of homing to the PNS. The expanded CD4 −8 − αβ T cells may have helper and effector functions, related to initiation of EAN in the CD4 −8 − mice. Lack of CD4 + and CD8 + expressing cells does not prevent the initiation of an autoimmune disease.

Inflammatory cells in experimental intervertebral disc injury.

Inflammatory cells were located by immunocytochemistry in areas of experimental intervertebral disc injury in pigs. To study the occurrence of T lymphocytes and macrophages 1 week, 1 month, and 3 months after partial-thickness transverse scalpel injuries in pig lumbar discs. Inflammatory cells and mediators recently have been observed in disc herniation tissue that was removed at disc prolapse surgery. The prevalence of inflammatory cell infiltrates in such clinical disc tissue material also has been studied. There are no studies, however, that have analyzed, using immunocytochemical methodology, the occurrence of, types of, and time dependence of inflammatory cells in an experimental disc injury model. The role of inflammation in intervertebral disc injury and repair has not been determined. Transverse scalpel injuries 5-mm long and 4-mm deep were cut in the anterolateral anulus of L5-L6 and L4-L5 discs in 16 pigs. The cuts in the center of the anulus did not reach the nucleus pulposus and never produced a disc prolapse. In every pig, two non-adjacent lumbar discs (L1-L2 and L2-L3) were used as controls. Four discs per animal were studied in parallel by two different complementary immunohistochemical staining protocols. T lymphocytes and macrophages were located immunohistochemically using CD3 and CD68 antibodies, respectively. Discs were removed for analysis from four pigs at 1 week, from six pigs at 1 month, and from six pigs at 3 months. Inflammatory cells were categorized by two independent observers as being entirely absent (-), only few scattered cells (+), and at least one larger cellular infiltrate (+2). In none of the discs could extensive inflammatory cell infiltration be observed. T lymphocytes were present in significantly more sections cut from injured discs than in sections cut from control discs. The difference was highly significant particularly at 1 week and 1 month after disc removal. Only the 1-month-after-injury sections from injured discs exhibited significantly more macrophages than those from control discs. The results suggest the presence of only modest inflammatory cell infiltration in experimental intervertebral disc injury at all follow-up times. The inflammatory response in partial-thickness anterior experimental intervertebral disc injury, in the absence of disc prolapse, seems to be dominated by a T lymphocyte response. The macrophage response is apparently strongest at 1 month after such injury. These findings differ from what has been observed in herniated disc tissue.

Mechanisms of inflammatory response in sympathetic ophthalmia and VKH syndrome.

Although the inciting events in the pathogenesis of sympathetic ophthalmia and Vogt-Koyanagi-Harada (VKH) syndrome are different, these two forms of bilateral, granulomatous uveitis share several clinical, histopathological and immunohistochemical features, including their association with HLA types and in their in vitro T-cell response to retinal antigens. These clinical and immunopathological features indicate that there is an underlying T-cell mediated autoimmunity to uveal/retinal antigens in the development of these forms of uveitis. Both forms exhibit preservation of the choriocapillaris and retina despite extensive inflammatory cell infiltration in the choroid. Recent experimental studies suggest that this preservation of choriocapillaris could be the result of anti-inflammatory products secreted by the retinal pigment epithelium, including transforming growth factor-beta and a novel protein called retinal pigment epithelial protective protein that is known to suppress the phagocyte generation of superoxide. Such suppression of the oxidant release in the choroidal inflammation could help protect the uvea from necrotic change and preserve the choriocapillaris from inflammatory cell infiltration.

Autoimmune Sjögren's-like lesions in salivary glands of TGF-beta1-deficient mice are inhibited by adhesion-blocking peptides.

The targeted disruption of the TGF-beta1 gene in mice (TGF-beta1 -/-) leads to extensive inflammation in vital organs, cachexia, and death within 3 to 4 wk. Significant inflammatory lesions develop initially in the periductal regions of the salivary glands and escalate as the animals become symptomatic. These inflammatory sites, characterized by lymphocytic infiltration and increased proliferation, cytokine mRNA expression, and IgG-positive cells, resemble lesions of Sjögren's syndrome. Moreover, the inflammatory pathology, enhanced MHC expression, and Ab production are consistent with an autoimmune-like etiology. Glandular atrophy and loss of acini with reduced saliva production appear to contribute to the wasting syndrome characteristic of the TGF-beta1 -/- mice. To determine whether the structural and functional defects were developmental due to the absence of TGF-beta1 or secondary to the inflammation, TGF-beta1 -/- mice were treated with synthetic fibronectin peptides, which block leukocyte infiltration. Daily systemic injections of RGD, CS-1, and/or peptides derived from the heparin-binding region of the A chain not only prevented leukocyte infiltration in the salivary glands of the TGF-beta1 -/- mice, but also reversed the acinar and ductal derangements. These data suggested that salivary gland development is not jeopardized in the absence of TGF-beta1, but that the extensive infiltration of inflammatory cells compromises glandular structure and function. The essential nature of TGF-beta1 in controlling inflammatory and immune processes is confirmed by these studies. Moreover, these TGF-beta1 -/- mice provide an important model of autoimmune disease that can be used in the design of therapeutic interventions.

A model of latent adenovirus 5 infection in the guinea pig (Cavia porcellus).

A model of adenovirus 5 (Ad5) infection was developed in guinea pigs to begin to study its role in the pathogenesis of peripheral lung inflammation. Forty animals were inoculated intranasally with 10(7.0) pfu of Ad5/animal, and 15 animals inoculated with sterile culture media served as controls. Viral titres were 10(4.4), 10(6.1), 10(5.2), and 10(2.9) pfu/animal, on days 1, 3, 4, and 7 after infection, respectively. In situ hybridization to viral DNA and immunocytochemistry for Ad5 E1A protein localized the virus to airway and alveolar epithelial cells. Histologic examination showed an extensive inflammatory cell infiltration around the airways, with epithelial necrosis and an alveolar exudate that caused localized alveolar collapse in the infected areas. Immunocytochemistry identified the cells in the infiltrate as cytotoxic T cells. Although all animals 20 and 47 days after infection had seroconverted to Ad5, virus was not detected in these groups either by viral plaque assay or in situ hybridization. Ad5 E1A DNA was detected by polymerase chain reaction in five of six animals 20 days after infection and in five of five animals 47 days after infection. In these same animals, E1A protein was detected 20 days after infection in two and 47 days after infection in one while persistent bronchiolitis was observed in four and three animals 20 and 47 days after infection, respectively. These results demonstrate that the guinea pig provides a useful model to study the role of Ad5 infection in chronic airway inflammation.

Lymphocyte subsets in immune-mediated otitis media with effusion.

To examine the role of T-cell subsets in immune-mediated otitis media with effusion induced by keyhole limpet hemocyanin (KLH), we used immunohistochemical methods to investigate the kinetics of immunocytes of the middle ear (ME) and eustachian tube (ET) in healthy BALB/c mice. Antibodies against murine macrophages and granulocytes (anti-Mac-1), helper T cells (anti-Lyt-1), suppressor T cells (anti-Lyt-2), immunoglobulins (anti-IgG, -IgM, -IgA), secretory component (SC) and KLH were used. The ME exhibited a substantial immune response, whereas the response of the ET was minor and was associated with a secondary ME immune response. After KLH challenge, an effusion with an extensive infiltration of inflammatory cells (Mac-1, IgG+ and IgM+ cells) was observed at days 1 and 3 in the ME cavity and rapidly disappeared by day 7. Within the ME mucosa, a large number of cells was observed at days 1 and 3, peaking on day 7 when a submucosal lymphoid infiltration was detected. In the immune response of the ME mucosa, Mac-1 cells were the predominant cell type followed by helper T cells, IgG+ cells, IgA+ cells and then IgM+ cells. Suppressor T cells were rarely detected after KLH challenge. SC was present within ME epithelial cells from days 1 to 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti—tumor necrosis factor therapy abrogates autoimmune demyelination

To define a role for the cytokine tumor necrosis factor (TNF) in immune-mediated demyelination, the effect of anti-TNF antibody was investigated with a form of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice induced by the adoptive transfer of myelin basic protein-(MBP)-sensitized T lymphocytes, an animal model of the human disease multiple sclerosis (MS). In three separate experiments, no mouse sensitized for EAE and then treated with anti-TNF by intraperitoneal injection developed signs of central nervous system (CNS) disease. Examination of CNS tissue from anti-TNF-treated animals showed no pathological changes. CNS tissue from control animals demonstrated extensive inflammatory cell infiltration and demyelination. To test whether anti-TNF therapy was inhibitory to encephalitogenic cells, preincubation of MBP-sensitized T lymphocytes with anti-TNF in vitro prior to injection into recipient mice was performed, and resulted in no diminution of their ability to transfer EAE. In addition, spleen cells from anti-TNF-treated mice were capable of serial transfer of EAE, similar to spleen cells from control animals. However, spleen cells from anti-TNF-treated mice did not produce TNF on stimulation with MBP or concanavalin A. This study showed that anti-TNF antibody can inhibit effectively the development of EAE by interfering with the effector, rather than the induction, phase of the disease. Anticytokine therapy may have important applications in the development of new therapeutic strategies for MS.

Gastric histology and plasma gastrin response to a meal in patients with duodenal ulcer disease after five years treatment with ranitidine

Fifty asymptomatic patients with duodenal ulcer disease, aged 31-82 years, who had received ranitidine maintenance therapy continuously for five or more years without a symptomatic recurrence, were studied. Fasting plasma gastrin concentrations were normal (mean 24 pmol/L, S.D. +/- 22) while the post-prandial gastrin response was variable with maximum plasma concentrations ranging from 16 to 309 pmol/L. Endoscopy revealed six asymptomatic peptic ulcers. Histological examination of gastric biopsies showed mild, superficial inflammatory cell infiltration of the fundic mucosa, but more extensive inflammatory cell infiltration with some atrophy of the mucosal glands in the antral mucosa. Patchy intestinal metaplasia was evident in the antral mucosa of 18 patients. No fundic ECL cell hyperplasia was seen. Helicobacter pylori were detected in the corpus and antrum of most patients. These results suggest that maintenance treatment with ranitidine for 5 years is not associated with either significant hypergastrinaemia or with changes in the fundic mucosa which could be interpreted as pre-malignant.

Membrane perturbations and mediation of gap junction formation in response to taurine treatment in normal and injured alveolar epithelia.

Nitrogen dioxide is an air pollutant that causes pulmonary alterations. Employing light and transmission electron microscopy, we examined plastic sections and freeze-fracture replicas of alveolar epithelium of groups of hamsters exposed to nitrogen for 24 h to determine taurine-induced changes in intercellular junctions. Prior to exposure, one group of hamsters was given 0.5% taurine in their drinking water for 2 weeks. A second group of hamsters was given taurine-free water. The taurine-treated group was divided into three subgroups. The first subgroup was exposed to nitrogen dioxide at a concentration of 7 ppm for 24 h, the second subgroup was exposed to nitrogen dioxide at a concentration of 30 ppm for 24 h, and the third subgroup was exposed to normal room air for 24 h. The nontaurine-treated animals were similarly divided into three subgroups and treated as described above. The lungs of the hamsters exposed to nitrogen dioxide without the taurine pretreatment exhibited extensive inflammatory cell infiltration in the walls of the terminal bronchioles, alveolar ducts, and peribronchiolar alveoli. The degree of infiltration was proportional to the degree of nitrogen dioxide concentration. The taurine-treated animals exposed to nitrogen dioxide and the nontaurine-treated animals exposed to room aid did not show any inflammatory infiltrate. Freeze-fracture replicas of the tight junctional regions of the type I and type II pneumocytes revealed significant fragmentation in the nitrogen dioxide-exposed lungs. It was also observed that the tight junctions between the type I pneumocytes of the taurine-treated groups, whether exposed or not, revealed gap junction-like aggregates among the tight junction fibrils. The 30-ppm nitrogen dioxide exposed group exhibited larger and more frequent gap junctions between the pneumocytes than those observed in the 7-ppm nitrogen dioxide exposed group. The evidence suggests that taurine may have an effect on plasma membranes and intercellular communications. Changes in intercellular communication may contribute to decreased susceptibility to injury and increased pneumocyte survival.

Sjögren's Syndrome with Multiple Bullae and Pulmonary Nodular Amyloidosis

We treated a patient with Sjögren's syndrome associated with multiple bullae and pulmonary nodular amyloidosis, both of which were identified by open lung biopsy. The mechanism of bullae formation appeared to be narrowing of the airway, as a result of extensive inflammatory cell infiltration to the bronchiolar wall, which acted as the check valve mechanism. We believe this to be the first reported case of Sjögren's syndrome accompanied by these two pulmonary manifestations.

Strawberry disease in rainbow trout, Salmo gairdneri Richardson

Abstract. Strawberry disease is a subchronic, non–debilitating, and non–fatal inflammatory skin disease of rainbow trout that has been recognized for the past 25 years. Morbidity ranges up to 80% and the disease affects fishes from 15cm in length to brood stock size. Epizootiological data indicate that strawberry disease usually appears, first in the autumn and reaches peak incidence during the following winter and spring. Data also indicate that the disease is found only in certain trout farms in the western and Pacific north–western regions of the United States. Although the cause of strawberry disease is unknown, the normal clinical course of 8 weeks can be reduced by oral treatment with oxytetracycline. Clinical signs include appearance of bright red, raised, circumscribed, ulcerated and indurated lesions in the skin that usually range up to 3 cm or more in diameter. Microscopically, the disease is characterized as a subchronic, focal, non–suppurative dermatitis with ulceration and extensive infiltration of mononuclear inflammatory cells.

Pathological features of multiple bone infection in the foal

The gross and histological features of multiple bone infection in two foals are described. In both cases the lesions were confined to the region of the growth plate. Bone and, in some cases, growth plate cartilage destruction has occurred associated with an extensive inflammatory cell infiltration. The significance of the pathological observation is discussed in relation to the pathogenesis of bone infection in the foal.

Arrest of myelination and demyelination in rabbit retina induced by herpes simplex virus infection.

Herpes simplex virus was injected into the vitreous of suckling and adult rabbits. In the suckling rabbits the infection caused an arrested myelination of the strip. Further, the infected strips showed degenerative changes with splitting and distension of myelin sheaths which then disintegrated. Ultrastructurally, herpes simplex virus particles were found in both oligodendroglial cells and in astrocytes in the bundles. No increase in intraocular pressure was recorded during the inflammation. The infection spread along optic pathways to the opposite side. Inflammatory cells appeared at the surface and infiltrated the degenerating strip. Especially in the contralateral eye, an extensive inflammatory cell infiltration was seen among bundles of nerve fibres which showed partly well-preserved myelin and partly with signs of demyelination reminiscent of the picture of experimental allergic encephalomyelitis in the epiretinal strip.

Pancreatitis of mice infected with encephalomyocarditis virus.

Morphologic changes in the pancreas of mice infected with encephalomyocarditis virus were studied to learn of the pathogenesis of viral pancreatitis. Viral crystals with associated cell injury including necrosis were noted in both acinar and islet cells of the pancreas of newborn and adult mice. Pathologic changes included scattered individual or focal cell necrosis of varying degrees of damage of both the acinar and islet cells. Mild to extensive inflammatory cell infiltration and edema were noted. It is suggested that the virus directly invaded the cells of parenchymatous tissue of the pancreas. A possible relationship between the damage noted and diabetes mellitus is discussed.