Ai. Medeiros et al., Leukotrienes are involved in leukocyte recruitment induced by live Histoplasma capsulatum or by the beta-glucan present in their cell wall, BR J PHARM, 128(7), 1999, pp. 1529-1537
1 The inflammatory cell influx towards the peritoneal cavity in mice inocul
ated i.p. with live or dead Histoplasma capsulatum or with its subcellular
preparations was studied. We also evaluated the effects of dexamethasone (D
exa) or MK886, an inhibitor of leukotriene (LT) biosynthesis, on the recrui
tment of leukocytes.
2 Live yeast form of fungus (LYH) induced an increase in neutrophils (NE) w
hich was highest 4 to 24 h after inoculation. Mononuclear cell (MN) migrati
on beginning at 24 h with a gradual increase over -18 and 168 h, and an eos
inophil (EO) recruitment occurs between 24 and 48 h.
3 NE and EO recruitment induced by dead mycelial form of fungus (DMH) was g
reater than that observed for dead yeast form of fungus (DYH). A similar le
ukocyte migration pattern was seen after i.p, injection of the alkali-insol
uble fraction (F1) from DYH (F1Y) and F1 from DMH (FIM) this being more act
ive 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 co
ntribute to NE and EO migration since the treatment with Dexa was more effe
ctive in inhibiting cell migration than MK886. Complement dependent leukocy
te migration may participate in this recruitment. Treatment with MK886 comp
letely abolished MN cell migration, indicating its dependence on the presen
ce of LT.