Differential release of MIP-1alpha and eotaxin during infection of mice by Histoplasma capsulatum or inoculation of beta-glucan.
OBJECTIVE
In the present study, we evaluated the levels of MIP-1alpha and eotaxin and in vivo migration in the peritoneal cavity model, in mice inoculated with live yeast forms of Histoplasma capsulatum or the beta-glucan cell wall component of this fungus, and the influence of a leukotriene biosynthesis inhibitor, MK886, on the release of these chemokines in relation to cell recruitment.


METHODS
Female outbred Swiss mice (N = 4-5 per group, 3-4 wk, were used. Mice were injected i.p. with 1 ml of the 6 x 10(5) live yeast form of the fungus or with 10 microg of beta-glucan from the cell wall fraction, and treated daily with MK886 (1 mg kg(-1), p.o.) or vehicle.


RESULTS
The fungus induced rapid generation of high levels of MIP-1alpha, which remained elevated from 4-48 h whereas very little eotaxin was detected at any time point (Fig. 1A and B). In contrast, the beta-glucan induced a little MIP-1alpha but considerably higher concentrations of eotaxin within the first four hours; however, the level of neither chemokine was sustained (Fig. 2A and B). Treatment of animals with MK886 was effective in reducing the numbers of neutrophils, eosinophils and, to a lesser degree, mononuclear cells accumulating in the peritoneal cavity in response to both the live fungus (Fig. 1C-E) and the cell wall beta-glucan (Fig. 2C-E).


CONCLUSIONS
The results suggest that chemokines and leukotrienes may play key roles in the inflammatory cell influx to H. capsulatum infection or to the inoculation of the beta-glucan cell wall component of this fungus
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
A I
AI
Medeiros
A
A
Malheiro
P J
PJ
Jose
D M
DM
Conroy
T J
TJ
Williams
L H
LH
Faccioli
D000818:Animals; D002473:Cell Wall / Q000737:chemistry; D054413:Chemokine CCL11; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000097:blood; D019742:Chemokines, CC / Q000378:metabolism*; D005260:Female; D006658:Histoplasma / Q000502:physiology*; D006660:Histoplasmosis / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects; D015289:Leukotrienes / Q000096:biosynthesis / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D051379:Mice; D013997:Time Factors; D047071:beta-Glucans / Q000008:administration & dosage* / Q000494:pharmacology*
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D019742:Chemokines, CC; D015289:Leukotrienes; D019402:Macrophage Inflammatory Proteins; D047071:beta-Glucans