Enhanced Superoxide Production by Rat Alveolar Macrophages Stimulated In Vitro With Biological Response Modifiers

Abstract

The kinetics of superoxide release and the effects of several biological response modifiers (BRM) on superoxide release from rat pulmonary alveolar macrophages (AM) have been studied. These cells produced superoxide anion both spontaneously and in response to phorbol myristate acetate (PMA) in a dose-related manner. The response to PMA peaked in approximately 2 hr and maintained plateau levels for an additional 2-3 hr before subsiding. Pretreatment of the macrophages in vitro with a number of immunostimulants enhanced the production of superoxide above that of controls. The release of superoxide in response to the immunostimulants was a slow phenomenon that took place over a 3-5 hr time period. Lymphokine-containing supernatants from concanavalin A (con A)-stimulated rat spleen cells (LK-Sup), murine recombinant gamma interferon (rMuIFN-gamma), nigeran, and muramyl dipeptide (MDP) enhanced this response in a dose-related manner. Poly I:C and Salmonella typhosa lipopolysaccharide (LPS) stimulated rat alveolar macrophages at low but not high concentrations. In contrast to the alveolar macrophages, rat peritoneal exudate cells were not activated by immunostimulants to produce increased amounts of superoxide.

Lipopolysaccharide stimulates alveolar macrophage adherencein vivo andin vitro

“…Since the media contained no serum, it appears that LPS acted directly on the cells. These findings are in agreement with observations that LPS stimulates AM in vitro to increase release of superoxide ion and induces release of interleukin-1 and tumor necrosis factor [8][9][10]. Our findings that LPS stimulates AM in vitro in the absence of serum suggest that the agent may act directly on AM in vivo.…”

“…We used comparatively large doses of LPS to maximize the effects on the cell. Interestingly, while some AM functions (such as LPS-induced increases in maximal release of superoxide ion) are sensitive to nanogram quantities of LPS [8], others (such as release of interleukin-1) require microgram amounts of LPS for significant stimulation to occur [9]. Our findings differ from those of Davis et al [14], who found that E. coli LPS at concentrations of 10gg/ml or higher inhibited adherence and spreading of human AM after 24 hours of incubation.…”

Subset-Specific Expression of Potassium Channels in Developing Murine T Lymphocytes

“…These results are summa-[n thymocytes with mature phenotypes, rized in the tentative lineage diagram in Fig. types of K+ channels expressed were 3D. ,hly correlated with cell-surface pheno-Our finding that immature thymocytes Ce, and hence with immunological fimcabundantly express type n K+ channels n. CD4+CD8thymocytes, primarily agrees well with previous results from patchcursors to helper T cells that recognize clamp studies of thymocytes from humans ss II antigens of the major histocompati- (18) and mice (19). These reports demonity complex (MHC) (15,16), displayed strate that n channels appear in the T lyme n channels at densities one-tenth to phocyte lineage before the onset of immut-fifth those of either of the itnmature nological competence (Fig.…”

“…3B). Excluding and I channels were not reported in an few cells in this class with unusually high earlier study of CD4-CD8+ thymocytes mbers of channels (gK> 3 nS), the aver- (19), probably because the particular experinormalized conductance was 0.40 ± mental protocols that distinguish amongthe 17 nS/pF (n = 20), corresponding to several classes of K+ channels were not used 1.2 n channels per square micrometer of (see Fig. 1).…”

Nitric oxide mediates murine cytomegalovirus-associated pneumonitis in lungs that are free of the virus.

“…While it was confirmed that various kinds of cytokines were produced in the lung of the MCMV infected mice when their T cells were activated in vivo, it is still unclear as to whether or not the cytokines injured the lung tissue directly or indirectly through the production of some biologically active substances. Among them, the oxygen and nitrogen radicals were reported to cause a severe inflammation, and moreover, both TNF-␣ and IFN-␥ are known to enhance the productions of these radicals (27)(28)(29)(30)(31)(32)(33). The production of these radicals were thus examined in the following experiments.…”