[Interactive laser cytometer/anchored cell analysis and sorting system].

Lipoxins (LX) are bioactive eicosanoids that carry a tetraene structure and serve as regulators of inflammation, in part by inhibiting neutrophil migration and adhesion. Lipoxin A4 is rapidly regulated by conversion to inactive LX metabolites via local metabolism that involves dehydrogenation as the predominant route. Here, several LXA4 analogs were designed that resisted rapid conversion by both differentiated HL-60 cells and recombinant 15-hydroxyprostaglandin dehydrogenase, systems where native LXA4 is degraded within minutes. The rank order of conversion by recombinant dehydrogenase was LXA4 methyl ester > PGE2 approximately PGE2 methyl ester > LXA4 >>> the novel LXA4 analogs. In addition, 15(R/S)-methyl-LXA4, 15-cyclohexyl-LXA4, and 16-phenoxy-LXA4 proved to retain LXA4 bioactivity and inhibited neutrophil transmigration across polarized epithelial cell monolayers as well as adhesion to vascular endothelial cells. These results indicate that LXA4 analogs can be designed using these criteria to resist rapid transformation and to retain biological actions of native LXA4. Moreover, the results suggest that LXA4 stable analogs can be useful tools both in vitro and in vivo to evaluate LXA4 actions and therapeutic potential.

Cell Adhesion↗

PubMed1995

A model for the initial phase of cell/surface interactions based on ligand binding phenomena.

The interaction between mammalian cells and solid surfaces plays an important role in a number of biological phenomena. Of particular clinical importance is the migration of cells suspended in blood to the wall of a blood vessel in the event of tissue damage. While the resultant inflammation often represents a desirable response to an external challenge, responses of this type can also lead to adverse consequences. Although the cell migration phenomenon is well known, a plausible mechanism for controlling the critical 'rolling' stages of adhesion has yet to be proposed. In this report we suggest how a simple consideration of ligand/receptor binding interactions can be used to explain a switch between a situation where a cell population is almost entirely in free suspension, to one where a significant fraction is attached to the solid surface.

Cell Adhesion↗

PubMed1995

Selective deactivation of human monocyte functions by TGF-beta.

TGF-beta at 1 and 10 ng/ml inhibited H2O2 production and fibronectin adherence by human monocytes. Coculture with anti-TGF-beta Abs or with IFN-gamma, but not with growth hormone, abrogated these effects. Neither viability nor superoxide production were decreased by TGF-beta treatment. TGF-beta appeared to be inhibiting H2O2 production rather than inducing catalase as preincubation in azide was without effect. Also, TGF-beta did not inhibit activity against virulent Mycobacterium tuberculosis. Coculture of monocytes with IFN-gamma + TGF-beta in vitro moderately inhibited the growth of M. tuberculosis when compared with untreated cells. Phagocytosis was not inhibited. Treatment of monocytes with another combination of cytokines, IFN-gamma+ TNF-alpha + vitamin D3, markedly reduced bacterial viability, although this appeared to be due to decreased phagocytosis leading to extracellular death of the bacteria. We conclude that despite suppressing some monocyte functions such as H2O2 production and adherence, TGF-beta, in combination with other cytokines, leaves other antimicrobial functions of the monocyte unaffected or even enhanced.

Cell Adhesion↗