Otto-Henning Wilhelms

Intratracheal Application of Sephadex in Rats Leads to Massive Pulmonary Eosinophilia without Bronchial Hyperreactivity to Acetylcholine

Fourteen Brown-Norway rats were pretreated with physiological saline (n = 7) or 500 micrograms Sephadex (n = 7) intratracheally. 24 h later, a bronchial provocation test was performed under pentobarbital anaesthesia using increasing doses of acetylcholine aerosol and the degree of bronchospasm was measured using a modified Konzett-Rössler method. Subsequently, leucocyte counts were determined in the bronchoalveolar lavage fluid (BALF), BALF cells were differentiated, and the chemiluminescence of the BALF leucocytes were measured. Finally, the lungs were removed and histologically examined. The cell count in the BALF was significantly (p less than 0.05) increased in the animals pretreated with Sephadex compared to those in the saline group (mean value +/- SEM: 0.38 +/- 0.07 vs. 0.15 +/- 0.02 x 10(6)/ml). This difference was also reflected in the chemiluminescence measurements (2.51 +/- 0.53 vs. 0.20 +/- 0.03 x 10(6) counts/0.5 ml). In the Sephadex-treated animals there was also a significant increase in the absolute number of neutrophil (0.040 +/- 0.010 vs. 0.011 +/- 0.002 x 10(6)/ml) and, in particular, eosinophil granulocytes (0.188 +/- 0.055 vs. 0.003 +/- 0.001 x 10(6)/ml) in the total leucocytes of the BALF. Lung histology showed massive perialveolar and peribronchial oedema and granulomatous infiltrates, primarily with eosinophils, after intratracheal application of Sephadex; these findings were not observed in the saline group. None of these changes in the rats pretreated with Sephadex manifested themselves in increased bronchial reactivity to acetylcholine aerosol. It is uncertain if the Sephadex-induced increase in the eosinophil count is accompanied by an activation of this cell population, which appears to be of importance for the occurrence of bronchial hyperreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro generation of smooth muscle-contracting leukotrienes from isolated epidermal cells.

Single-cell suspensions of murine and human epidermal cells were studied for the presence of peptidoleukotrienes (LTs), using in vitro guinea pig ileum contraction as bioassay and a commercial radioimmunoassay. The calcium ionophore A23187 at 5 x 10(-6) M alone or in combination with arachidonic acid at 10(-4) M caused release of LTC4/D4 within 10-30 min and for up to 18 h. LTB4, as was measured in the chemotaxis assay, was released at different levels and with different kinetics from the same cells. Epidermal cells may thus regulate cutaneous inflammation by secreting potent vasoactive and muscle-contracting in addition to chemotactic lipid mediators.