CORRELATION BETWEEN INFLAMMATORY CELLULAR-RESPONSES AND CHEMOTACTIC ACTIVITY IN BRONCHOALVEOLAR LAVAGE FLUID FOLLOWING INTRATRACHEAL INSTILLATION OF NICKEL SULFATE IN RATS

In a preceding study, we reported that the numbers of macrophages and polymorphonuclear leukocytes (PMN) were increased in bronchoalveolar lavage fluid (BALF) following the intratracheal instillation of nickel sulfate (NiSO4) in rats. In the present study, BALF chemotactic activities for both macrophages and PMN were measured to investigate if the increases of these inflammatory cells in BALF depend on increases in chemotactic activities in epithelial lining fluid (ELF) of the lung. Both the number of PMN and the PMN chemotactic activity peaked at 2 days post-instillation and they were significantly correlated. However, the PMN chemotactic activity was inversely correlated with concentration of leukotriene B-4 (LTB(4)), a well-known chemotaxin. Although PMN were not observed in control BALE LTB(4) concentration in the control ELF (ca. 5 x 10(-7) M) was estimated to have a potential to attract PMN chemotactically through a membrane in in vitro migration assay. These results suggest that the presence of LTB(4) in ELF itself does not trigger transpulmonary PMN infiltration. The rat BALE were fractionated by high performance liquid chromatography (HPLC), and PMN chemotactic activity of each fraction was measured. The elution profiles of PMN chemotactic activity showed that there were at least two different chemotaxins in BALF obtained from the NiSO4-exposed rats. Macrophage chemotactic activity in BALF also peaked at 2 days post-instillation. However, the number of macrophages was not significantly correlated with the chemotactic activity for macrophage in BALE The HPLC study showed that the macrophage chemotactic substance in the BALE obtained from NiSO4-exposed rats was different from complement fragment (C5a) and its MW was estimated to be 10-12 kD.