Relationships between the structure and function of lipopolysaccharide chemotypes with regard to their effects on the human polymorphonuclear neutrophil |
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Authors: | C Pugliese M D LaSalle V A DeBari |
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Affiliation: | Department of Biology, Seton Hall University, South Orange, New Jersey. |
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Abstract: | Polymorphonuclear neutrophils (PMN), harvested from healthy volunteers, were challenged with endotoxins from Salmonella minnesota smooth-strain and rough-strain mutants (Ra, Rb2, RcP-, Rd1P- and Re) as well as with lipid A in an effort to determine the relationship between lipopolysaccharide (LPS) structure and its ability to affect PMN chemotaxis (CT), random migration (RM) and luminol-dependent chemiluminescence (CL). In the presence of untreated autologous serum (UAS), as has been previously demonstrated for CL, CT in a modified Boyden chamber is stimulated but no significant differences among the chemotypes were observed. In the presence of heat inactivated autologous serum (IAS), significant variations among the LPS chemotypes occurred. Also noteworthy was the observation that, although the total number of cells migrating across the membrane was similar for both UAS and IAS, UAS promoted PMN migration beyond the membrane into the chamber, as opposed to IAS which caused the cells to remain adherent to the distal face of the membrane. In the absence of serum, RM was inhibited in a dose-dependent fashion by LPS from lipid A and the rough-strain mutants, with the degree of inhibition being progressively greater with increasing molecular complexity of the chemotype LPS. The smooth-strain LPS exerted an intermediate effect. In the case of CL, lipid A was the most potent stimulus, with the response decreasing as molecular complexity increased up to RcP-; the remaining core mutant LPS provided slightly greater responses. The LPS from the smooth-strain promoted a response similar to the response to Ra LPS. Based on these data, it is concluded that there are qualitative as well as quantitative effects of the carbohydrate moieties of LPS. These data also suggest that while LPS may provoke active migration in the circulation during endotoxemia, infection localized in tissue might bring about an inhibition of PMN migration while allowing the PMN to mount an oxidative response. |
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