Leukotrienes are involved in leukocyte recruitment induced by live Histoplasma capsulatum or by the beta-glucan present in their cell wall

Br J Pharmacol. 1999 Dec;128(7):1529-37. doi: 10.1038/sj.bjp.0702912.


1. The inflammatory cell influx towards the peritoneal cavity in mice inoculated i.p. with live or dead Histoplasma capsulatum or with its subcellular preparations was studied. We also evaluated the effects of dexamethasone (Dexa) or MK886, an inhibitor of leukotriene (LT) biosynthesis, on the recruitment of leukocytes. 2. Live yeast form of fungus (LYH) induced an increase in neutrophils (NE) which was highest 4 to 24 h after inoculation. Mononuclear cell (MN) migration beginning at 24 h with a gradual increase over 48 and 168 h, and an eosinophil (EO) recruitment occurs between 24 and 48 h. 3. NE and EO recruitment induced by dead mycelial form of fungus (DMH) was greater than that observed for dead yeast form of fungus (DYH). A similar leukocyte migration pattern was seen after i.p. injection of the alkali-insoluble fraction (F1) from DYH (F1Y) and F1 from DMH (F1M) this being more active than former. The difference in concentration of beta-glucan in DYH and DMH could explain the different inflammatory capacity exhibited by the two forms of H. capsulatum. 4. LT seems to be the principal mediator of leukocyte migration in response to LYH, DYH or DMH or to beta-glucan. However, other mediators appear to contribute to NE and EO migration since the treatment with Dexa was more effective in inhibiting cell migration than MK886. Complement dependent leukocyte migration may participate in this recruitment. Treatment with MK886 completely abolished MN cell migration, indicating its dependence on the presence of LT.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Cell Wall / immunology
  • Cell Wall / metabolism
  • Chemotaxis, Leukocyte* / drug effects
  • Dexamethasone / pharmacology
  • Female
  • Glucans / immunology*
  • Glucans / metabolism
  • Histoplasma / immunology*
  • Histoplasma / metabolism
  • Histoplasmosis / immunology
  • Histoplasmosis / microbiology
  • Indoles / pharmacology
  • Leukocytes / drug effects
  • Leukocytes / microbiology*
  • Leukotriene Antagonists / pharmacology
  • Leukotrienes / biosynthesis
  • Leukotrienes / metabolism
  • Leukotrienes / physiology*
  • Mice
  • Neutrophil Infiltration / drug effects


  • Anti-Inflammatory Agents
  • Glucans
  • Indoles
  • Leukotriene Antagonists
  • Leukotrienes
  • MK-886
  • Dexamethasone