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Biomedical subjects

M D Rossman

Publications and source records attributed to M D Rossman.

66 records · Page 4Linked to original sources

Pulmonary sarcoidosis: correlation of serum angiotensin-converting enzyme with blood and bronchoalveolar lymphocytes.

Blood and bronchoalveolar (BA) cell populations were compared with serum angiotensin-converting enzyme activity (SACE) in 22 smoking and nonsmoking patients with recently diagnosed or active sarcoidosis. There was no correlation between SACE and blood lymphocyte populations, but a significant correlation was found between the number of BA lymphocytes and SACE and the number of BA T cells and SACE. In no case was SACE elevated when the number of BA lymphocytes was normal, but in 10 patients with increased numbers of BA lymphocytes SACE was normal. In fact, SACE was increased in less than one-third (7/22) of the patients. These results suggest that both SACE and the number of lymphocytes in lavage fluid reflect the intensity of the lung's inflammatory response in sarcoidosis but that quantification of BA lymphocytes is a more sensitive measure than SACE of active pulmonary sarcoidosis.

Bronchi↗

Inhibition of human lung fibroblast growth by mononuclear cells.

We examined in vitro the effect of supernatants from unstimulated, mitogen-stimulated and antigen-stimulated blood mononuclear cells on the growth of fibroblasts from normal adult lungs. Supernatants prepared from mononuclear cells in the absence of mitogen or antigen had no consistent effect on fibroblast growth. Supernatants from mononuclear cells incubated with antigens to which the donor was not sensitive (stimulation index, less than 5) also had no effect on fibroblast proliferation. In contrast, mitogen-stimulated (phytohemagglutinin, concanavalin A, pokeweed mitogen) and antigen-stimulated (purified protein derivative, beryllium sulfate) mononuclear cells (stimulation index greater than 5) inhibited log phase fibroblast growth. The inhibition was mediated by a soluble factor (or factors) that was elaborated within 24 h of initiation of mononuclear cell cultures. The factor was nondialyzable, partially heat labile, and its effect on fibroblast growth may be mediated in part by fibroblast prostaglandin production. The results suggest that inhibition of fibroblast growth by stimulated mononuclear cells may be an important mechanism regulating fibrosis in the lung.

Antigens↗

Pulmonary defense mechanisms: modulation of Fc receptor activity in alveolar macrophages and other phagocytic cells by N-formyl peptides.

Because the synthetic N-formyl peptides are similar in structure to products of bacterial metabolism, they may act similarly in providing signals of bacterial infection to phagocytic cells. With this in mind, we attempted to find out if N-formyl peptides increased Fc receptor activity in guinea pig alveolar macrophages, peritoneal macrophages, and neutrophils. N-formyl-methionyl-phenylalanine (FMP) and N-formyl-methionyl-L-leucyl-L-phenylalanine (FMLP) increased alveolar macrophage Fc receptor activity by 40 to 100%. The maximal increase in alveolar macrophage Fc receptor activity occurred after 2 h of in vitro incubation with 10(-6) M FMP. The increase in Fc receptor activity was blocked by cytochalasin B but not by colchicine, and did not appear to be related to morphologic alterations that were also induced by FMP. There was a similar increase in Fc receptor activity in peritoneal macrophages and neutrophils after in vitro exposure to FMP. For neutrophils, the increase was greatest after a 1-h incubation and with 10(5) M FMP. These results indicate that N-formyl peptides are stimulants of guinea pig phagocytic cell Fc receptor activity. Stimulation of Fc receptor activity may be one mechanism by which phagocytic cells combat bacterial infection in vivo.

Animals↗

Bronchoalveolar lavage in a patient with chronic berylliosis: evidence for hypersensitivity pneumonitis.

Because immunologic mechanisms are thought to have a role in chronic berylliosis, we studied the immunologic properties of peripheral blood and bronchoalveolar lymphocytes in a patient with this disease. Although the percent of peripheral blood T cells was slightly reduced compared with that in controls (59% versus 70%), there was a large increase in the number and proportion (94% versus 62%) of bronchoalveolar T cells. The percent of activated bronchoalveolar T cells was nearly five times the control value (64.5% versus 14%). Both peripheral blood and bronchoalveolar lymphocytes proliferated in response to BeSO4 and BeF2 exposure but the response of bronchoalveolar lymphocytes was greater than comparable numbers of peripheral blood lymphocytes. These findings are consistent with the concept that chronic berylliosis is a form of hypersensitivity pneumonitis and that bronchoalveolar lavage may be helpful in establishing the diagnosis of this disease.

Adult↗

Nodular endobronchial sarcoidosis: a study comparing blood and lung lymphocytes.

Patients with active sarcoidosis have a depression in systemic cell-mediated immunity manifested by lymphopenia, a reduction in circulating T cells, and impaired responses of these cells to polyclonal mitogens and recall antigens. Studies of bronchoalveolar cells (BA) have disclosed characteristic changes in lymphocyte populations that are opposite to what is found in peripheral blood. Since previous lavage studies have not specifically addressed endobronchial disease, we present results of peripheral blood (PB) and BA lymphocyte studies in a patient with acute pulmonary sarcoidosis who had gross endobronchial nodules. The lymphocytosis in the BA air space of this patient was greatly increased compared with patients with newly diagnosed sarcoidosis but no overt endobronchial disease. Cell surface markers, morphology, and in vitro proliferative response indicated that the BA lymphocytes were stimulated and more reactive than PB lymphocytes, suggesting a local immune inflammatory response. Bronchial biopsy specimens showed mononuclear cell infiltration of the epithelium overlying the inflammatory nodules. The biopsy examination and great increase in lymphocytes recovered from the airways suggest that the bronchi were a source of the BA lymphocytes. Since clinically inapparent bronchial involvement is frequent in sarcoidosis, inflamed bronchi may also be a source of BA lymphocytes in the absence of conspicuous endobronchial nodules.

Adult↗

Immunologic abnormalities in sarcoidosis.

Patients with active sarcoidosis (acute and chronic) have a depression in systemic cell-mediated immunity manifested by a reduction in the number of circulating T cells and impaired responses of these cells to polyclonal mitogens and recall antigens. These abnormalities are absent in patients with resolved disease and contrast with heightened B-cell activity. The latter includes elevated serum immunoglobulins and the presence of autoantibodies and circulating immune complexes. Similarly, many humoral abnormalities (for example, immune complexes) are absent in patients with resolved disease. Studies of bronchoalveolar cells have revealed changes that are opposite to what is found in peripheral blood. The number of lymphocytes recovered by bronchoalveolar lavage is increased. This is mainly due to an increase in the number of T cells and a subpopulation of activated T cells. These findings suggest that the lung (when involved) is the site of an immune inflammatory response.

Antibody Formation↗

Experimental silicosis: morphologic and biochemical abnormalities produced by intratracheal instillation of quartz into guinea pig lungs.

Six months after intratracheal instillation of silica, histologic, ultrastructural, cytologic, and biochemical studies were performed on the lungs of guinea pigs. The tissue response consisted of both diffuse alveolar septal infiltration with interstitial fibrosis and granulomatous infiltration with nodular fibrosis. Ultrastructural studies confirmed the presence of a mixed inflammatory exudate in the alveolar interstitium (histiocytes, neutrophils, eosinophils, and lymphocytes) and the Type II lining of cell hyperplasia. The number of lung cells recovered by lavage and the proportions of neutrophils and multinucleated cells in bronchoalveolar cells were significantly greater in experimental animals (P < .05) than in controls (intratracheal saline). Total lung collagen and collagen synthesis by cultured lung tissue were also increased in the experimental animals. Since the response of guinea pig lung to intratracheal silica included pathologic features common to human silicosis and idiopathic pulmonary fibrosis, this model has the potential for improving our understanding of both of these important clinical disorders.

Animals↗

Bronchoalveolar cell populations in acute sarcoidosis. Observations in smoking and nonsmoking patients.

Bronchoalveolar cells were obtained by segmental lung lavage from 14 patients with sarcoidosis and studied to determine changes in composition associated with acute disease and smoking history. In nonsmoking patients, both the proportion and number of lymphocytes recovered were significantly increased compared to nonsmoking controls (p less than 0.001 in both cases). Furthermore, the number of T cells was increased (4.19 +/- 0.72 vs. 0.896 +/- 0.107 x 10(6) cells/100 ml, p less than 0.001), and activated T cells were also increased (1.04 +/- 0.478 vs. 0.148 +/- 0.032 x 10(6) cells/100 ml, p less than 0.01). Less striking differences in these values were found when smoking sarcoid patients were compared to smoking controls, but there were no significant differences in these values for smoking and nonsmoking patients (p greater than 0.05). Thus acute sarcoidosis in both smoking and nonsmoking patients appears to be associated with a lymphocytosis of the bronchoalveolar space which results from increased numbers of T cells and activated T cells. The potential importance of this finding with regard to diagnosis and pathogenesis is discussed.

Acute Disease↗

Identification of activated T cells in sarcoidosis.

When peripheral blood lymphocytes are stimulated by mitogens or allogeneic cells, they acquire the capacity to form stable rosettes at 37 degrees C with sheep red blood cells, thereby identifying a population of activated T cells. In 7 consecutive patients with acute sarcoidosis, there was a significant (P less than 0.005) increase in the proportion and the total number of peripheral blood lymphocytes forming stable rosettes at 37 degrees C compared to age-matched normal control subjects (mean +/- SE, 12.6 +/- 3.0 versus 2.0 +/- 0.3 per cent, respectively). This occurred despite a significant decrease in the total number of lymphocytes (P less than 0.01) and T cells (P less than 0.001) in the peripheral blood in these same patients. Light and electron microscopic examination of sarcoid lymphocytes confirmed that cells forming stable rosettes at 37 degrees C were activated or atypical. Thus, in acute sarcoidosis, activated T cells are increased, whereas the total number of T cells is decreased in peripheral blood. This finding also posed certain technical problems in identifying B cells by surface immunoglobulin and complement receptors. Measures to overcome these difficulties are discussed. As determined by 2 independent tests of B cells (i.e., complement receptor and surface immunoglobulin), the number of circulating B cells was decreased.

Acute Disease↗

Immune complexes in sarcoidosis: a correlation with activity and duration of disease.

Samples of serum from patients with sarcoidosis were examined for the presence of immune complexes, using the Raji cell line. An indirect immunofluorescent technique was used to detect the binding of immune complexes to the complement receptors of Raji cells. Preliminary studies indicated that the method was sensitive and specific. We studied 44 patients with sarcoidosis who were separable into the following three distinct clinical groups: (1) acute disease (one year or less); (2) chronic active disease (five years or more); and (3) resolved disease (five years or more). In the 26 patients with acute disease, 12 had circulating immune complexes; immune complexes were present in two of the ten patients with chronic active disease. In contrast, immune complexes were absent in patients with resolved disease and normal control subjects. In patients with active disease, there was no apparent correlation between the presence of immune complexes and the stage of disease; however, immune complexes were present in five of the 11 patients with extrapulmonary disease, in seven of 12 patients with elevated concentrations of gamma-globulin, and in four of five of those patients with autoantibodies to lymphocytes.

Acute Disease↗