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Neutrophil migration induced by staphylococcal enterotoxin type A in mice: a pharmacological analysis
I A Desouza1, G Ribeiro-DaSilva
1Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, SP, Brazil.
Abstract:
Staphylococcal enterotoxin type A induced marked neutrophil migration into the mouse peritoneal cavity and was dependent on the number of resident macrophages. This migratory response was dose- (16-64 microg of staphylococcal enterotoxin type A/cavity) and time-dependent, peaking at 12 h and disappearing after 72 h. Dexamethasone (0.5 mg/kg) inhibited the neutrophil migration induced by staphylococcal enterotoxin type A (32 microg; 42% inhibition). A similar response was observed with the platelet-activating factor-acether receptor antagonist, BN 52021 (ginkgolide B, 3-(1,1-dimethylethyl)-hexahydro-1,4-7b-trihydroxy-8-methyl-9H-1,7alph a (epoxymethano-1H,6alphaH-cyclopenta (c) furo (2,3-b) furo (3', 2': 3,4) cyclopenta (1,2-d) furan-5, 9, 12 (4H)-trione); 10 mg/kg; 57% inhibition), the histamine H2 receptor antagonist, cimetidine (2 mg/kg; 31% inhibition), the lipoxygenase inhibitor, BWA4C (N-(3-phenoxycinnamyl) acetohydroxamic acid); 10 mg/kg; 73% inhibition), and capsaicin (trans-8-methyl-N-vanillyl-6-nonamide), a sensory C-fiber neuropeptide depletor. In contrast, indomethacin (5 mg/kg) had no effect on staphylococcal enterotoxin type A-induced chemotaxis. We conclude that the peritonitis induced by staphylococcal enterotoxin type A in mice is macrophage-dependent. The mechanism whereby staphylococcal enterotoxin type A stimulates macrophages to induce neutrophil recruitment remains to be elucidated.
Insights
Staphylococcal enterotoxin type A triggers neutrophil migration in mice, a process dependent on macrophages. Several inhibitors blocked this response, suggesting complex inflammatory pathways.
Area of Science:
- Immunology
- Microbiology
Background:
- Staphylococcal enterotoxin type A (SEA) is a potent exotoxin produced by Staphylococcus aureus.
- SEA is known to cause food poisoning and toxic shock syndrome.
- The mechanisms underlying SEA-induced inflammation, particularly neutrophil recruitment, are not fully understood.
Purpose of the Study:
- To investigate the role of resident macrophages in SEA-induced neutrophil migration.
- To identify potential inflammatory mediators involved in SEA-induced peritonitis.
Main Methods:
- Induction of peritonitis in mice using SEA.
- Administration of various pharmacological inhibitors (dexamethasone, BN 52021, cimetidine, BWA4C, capsaicin, indomethacin).
- Quantification of neutrophil migration into the peritoneal cavity.
Main Results:
- SEA induced significant neutrophil migration in a dose- and time-dependent manner.
- Dexamethasone, BN 52021, cimetidine, BWA4C, and capsaicin all inhibited SEA-induced neutrophil migration.
- Indomethacin had no significant effect on the observed neutrophil migration.
Conclusions:
- Macrophage-dependent mechanisms are crucial for SEA-induced peritonitis.
- Inflammatory mediators modulated by glucocorticoids, PAF, histamine, lipoxygenase, and C-fiber neuropeptides play a role in SEA-induced neutrophil recruitment.
- The precise molecular pathways by which SEA stimulates macrophages to recruit neutrophils require further investigation.