Anders Eklund

Stimuli-induced superoxide radical generation in vitro by human alveolar macrophages from smokers: Modulation by n-acetylcysteine treatment in vivo

Bronchoalveolar lavage (BAL) was performed on nine healthy nonsmoking subjects and on 11 healthy smokers; in the last mentioned group lavage was performed before and after eight weeks treatment with N-acetylcysteine (NAC; 200 mg t.i.d.). The BAL cells were cultured for 2 h or overnight. Adherent cells were examined for their capacity to generate superoxide radicals (determined by superoxide dismutase (SOD)-inhibitable cytochrome C-reduction) at stimulation with phorbol 12-myristate 13-acetate (PMA), serum-treated zymosan (STZ), the calcium ionophore A23187, or the chemotactic tripeptide formyl-methionylleucylphenylalanine (FMLP). Cells from nonsmokers responded with a very low degree of O(2)-generation to any of the stimuli employed whether cultured for 2 h or overnight. Cells from smokers also responded with low O(2)-generation after 2 h of culture. However, cells from smokers cultured overnight responded with marked O(2)-generation to PMA and STZ but the responses to FMLP and A23187 were low. NAC-treatment of the smokers resulted in a reduced degree of both PMA- and STZ-induced O(2)-generation in five individuals. In two other subjects, PMA-induced (but not STZ-induced) O(2)-generation was reduced. Two individuals showed increased O(2)-generation to PMA- and to STZ-stimulation after NAC-treatment. Mean values of O(2)-generation induced by A23187 or by FMLP were significantly reduced for cells harvested after NAC-treatment. Mean values for PMA-induced O(2)-generation also tended to be reduced by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of fibronectin and its degradation products in bronchoalveolar lavage fluid.

In order to estimate, in sarcoidosis, the extent of degradation and the availability of functionally active fibronectin (FN) in the alveolar space, native and total (= native + degraded) FN were determined in the bronchoalveolar lavage (BAL) fluid of 28 non-smoking patients with sarcoidosis, 12 healthy non-smokers and 24 asymptomatic smokers. The FN was measured in unconcentrated BAL fluid in the presence of the protease inhibitor aprotinin: total FN was assayed by a double-antibody sandwich enzyme-linked immunoadsorbent assay (ELISA) and native FN by a gelatin-antibody sandwich ELISA. Both in controls and in sarcoid patients, concentrations of native FN were lower than those of total FN, indicating that FN is degraded in the alveolar space. Compared to non-smoking controls, the sarcoid patients had significantly increased concentrations of both native and total FN (p less than 0.001 for both) in the BAL fluid. Native FN in percentage of total FN was similar in non-smoking sarcoids and controls, representing about 80% and 70%, respectively. In contrast, native FN corresponded to only 30% in the group of control smokers, indicating higher degradation in smokers. Thus, in smokers, less intact collagen-binding FN is available for forming an extracellular matrix, which may be necessary for repair. On the other hand, the elevation of FN, especially in its native form, in sarcoidosis implies that more of it may be available for repair but, if in excess, also for the build-up of fibrotic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

99mTc-DTPA clearance measured by a dual head gamma camera in healthy subjects and patients with sarcoidosis

Abstract99mTc-DTPA clearance was studied in ten healthy non smokers, five asymptomatic smokers and nine non smoking patients with sarcoidosis in the supine position with a dual head gamma camera allowing simultaneous information of regional clearance rates in frontal and dorsal projections. In the patients with sarcoidosis, a bronchoalveolar lavage was performed prior to the clearance study. DTPA clearance rate was measured during 60–90 min and data were corrected for recirculating radioactivity. The coefficients of variation for measurements on 2 consecutive days in the 10 healthy non smokers were 9%–11% for the right and left lung, anterior and posterior projections. The T1/2 calculated from total lung projections were 90–92 min for the anterior view and 84–85 min for the posterior view. Regional measurements did not add further information. No apico-basal difference was found but there was a significant fronto-dorsal gradient in99mTc-DTPA clearance in the supine position. Smokers had significantly (P<0.01) faster clearance rates (T1/2 28±10 min) than healthy controls. In the sarcoidosis group clearance rates were increased in four patients and no relationships were found between DTPA clearance rates and inflammatory markers (lymphocytes, albumin, ACE) in the bronchoalveolar lavage fluid.