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Granulocyte activation by endotoxin. I. Correlation between adherence and other granulocyte functions, and role of
Abstract:
Reminiscent of high concentrations of formylated chemotactic peptides, another group of bacteria-derived products, the lipopolysaccharides and lipid A, stimulate PMN adherence to petri dishes. Attachment and spreading of PMN is accompanied by intense release of secondary granule constituents and marked stimulation of the hexose monophosphate shunt activity. Dose-response studies with endotoxin preparations of diverse activity show that induction of PMN adherence, enzyme release, and respiratory burst activation are highly correlated, suggesting that this functional triad is mediated by a common mechanism. Hyperadhesiveness inducing concentrations of the chemotactically inert endotoxin lead to marked inhibition of PMN migration without affecting the direction-finding mechanism of the cell toward formylated peptides and C-derived chemotaxin(s). Endotoxin preparations at a lower grade of aggregation are more active, and the polysaccharide chains of the molecule are not essential with respect to PMN stimulation. Under our experimental conditions, endotoxin-induced stimulation of PMN is not inhibited by indomethacin, suggesting independence of cyclooxygenase-derived products. This type of PMN activation may play an important role in endotoxin-mediated tissue damage in vivo. Furthermore, hyperadhesion-induced inhibition of PMN migration to inflammatory sites during endotoxemia might hamper host resistance.
Insights
Bacteria-derived lipopolysaccharides and lipid A activate polymorphonuclear leukocytes (PMNs), increasing their adherence and degranulation. This endotoxin-induced PMN activation may contribute to tissue damage and impair host resistance during infections.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Bacteria-derived products like lipopolysaccharides (LPS) and lipid A are known to interact with host immune cells.
- Polymorphonuclear leukocytes (PMNs) are critical components of the innate immune system, involved in pathogen clearance and inflammation.
Purpose of the Study:
- To investigate the effects of lipopolysaccharides and lipid A on PMN function.
- To elucidate the mechanisms underlying endotoxin-induced PMN activation and its consequences.
Main Methods:
- Stimulation of PMNs with bacterial endotoxin preparations.
- Assessment of PMN adherence, degranulation, hexose monophosphate shunt activity, and migration.
- Dose-response studies with endotoxin preparations of varying activity and aggregation states.
Main Results:
- Lipopolysaccharides and lipid A significantly stimulate PMN adherence, degranulation, and hexose monophosphate shunt activity.
- PMN activation, enzyme release, and respiratory burst are highly correlated, suggesting a common underlying mechanism.
- High concentrations of endotoxin inhibit PMN migration without affecting chemotaxis, and polysaccharide chains are not essential for PMN stimulation.
Conclusions:
- Endotoxin-induced PMN hyperadherence and activation represent a significant pathway in endotoxin-mediated tissue damage.
- Inhibition of PMN migration during endotoxemia may compromise host resistance to infection.