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Published on: September 20, 2019
Endotoxin-induced selective dysfunction of rabbit polymorphonuclear leukocytes in response to endogenous chemotactic
Abstract:
To assess the mechanism and specificity of polymorphonuclear leukocyte (PMN) dysfunction induced by endotoxin, rabbits were injected intravenously with 100 micrograms of Escherichia coli endotoxin, and PMN function was studied 18 to 24 h later. Compared to PMN from normal rabbits, peripheral blood PMN from rabbits injected with endotoxin showed diminished chemotactic responsiveness to two endogenous peptides, C5a (complement) and platelet-derived growth factor, and to two endogenous lipids, leukotriene B4 and platelet-activating factor. The chemotactic response to the synthetic chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), was unimpaired. In contrast to migration, endotoxin injection resulted in inhibition of the secretory response to the two endogenous peptides but not to the lipids or to FMLP. At a 1:4 (vol/vol) dilution, the plasma either 1 or 24 h after the endotoxin injection inhibited normal PMN chemotactic responses to C5a but not to FMLP. Similarly, at a 1:10 dilution, this plasma inhibited normal PMN chemotactic responses to leukotriene B4. The factor responsible for inhibiting responses to leukotriene B4 was anionic, specific for leukotriene B4 responses, and greater than 12,000 daltons. These data may be relevant to understanding PMN dysfunction during gram-negative sepsis.
Insights
Endotoxin impairs polymorphonuclear leukocyte (PMN) function, specifically their response to certain peptides and lipids. This dysfunction may contribute to issues seen during gram-negative sepsis.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Polymorphonuclear leukocytes (PMNs) are crucial for immune response.
- Endotoxin, a component of gram-negative bacteria, can induce immune dysfunction.
- Understanding PMN dysfunction is vital for treating sepsis.
Purpose of the Study:
- To investigate the mechanism and specificity of PMN dysfunction caused by endotoxin.
- To identify how endotoxin affects PMN chemotaxis and secretion.
- To characterize factors in plasma that contribute to endotoxin-induced PMN impairment.
Main Methods:
- Rabbits were injected with Escherichia coli endotoxin.
- PMN function (chemotaxis, secretion) was assessed 18-24 hours post-injection.
- Plasma from endotoxin-injected rabbits was tested for its effect on normal PMN function.
Main Results:
- Endotoxin-injected rabbits showed reduced PMN chemotaxis to C5a, platelet-derived growth factor, leukotriene B4, and platelet-activating factor, but not FMLP.
- Endotoxin inhibited PMN secretion in response to peptides but not lipids or FMLP.
- Plasma from endotoxin-injected rabbits inhibited normal PMN chemotaxis to C5a and leukotriene B4.
Conclusions:
- Endotoxin induces specific PMN dysfunction affecting chemotaxis and secretion.
- A plasma factor, anionic and >12,000 daltons, inhibits leukotriene B4 responses.
- These findings offer insights into PMN dysfunction during gram-negative sepsis.
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