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Impairment of neutrophil migration to remote inflammatory site during lung histoplasmosis.

Medeiros AI, Secatto A, Bélanger C, Sorgi CA, Borgeat P, Marleau S, Faccioli LH - Biomed Res Int (2015)

Bottom Line: Our results show that pulmonary Hc infection impairs LTB4- or PAF-stimulated PMN recruitment to air pouch.Yet, remote inflammation did not modify PMN numbers in the bronchoalveolar lavage fluid (BALF) of Hc-infected mice.Along that line, our results show that PAF-elicited PMN chemotaxis was abrogated in 5-lipoxygenase-deficient animals.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Sciences, UNESP, 14801-902 Araraquara, SP, Brazil.

ABSTRACT
Histoplasma capsulatum (Hc) induces a pulmonary disease in which leukotrienes promote activation and recruitment of effectors cells. It is also well-recognized that leukotriene B4 (LTB4) and platelet-activating factor (PAF) induce leukocyte recruitment to inflammatory sites. We investigated the impact of pulmonary Hc infection on PMN migration to a remote inflammatory site. Our results show that pulmonary Hc infection impairs LTB4- or PAF-stimulated PMN recruitment to air pouch. Yet, remote inflammation did not modify PMN numbers in the bronchoalveolar lavage fluid (BALF) of Hc-infected mice. Interestingly, the concomitant administration of PAF and LTB4 receptor antagonists inhibited PMN recruitment to both BALF and the remote site, demonstrating cooperation between both mediators. Along that line, our results show that PAF-elicited PMN chemotaxis was abrogated in 5-lipoxygenase-deficient animals. These results suggest caution in the indiscriminate use of anti-inflammatory drugs during infectious diseases.

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Related in: MedlinePlus

Effect of SR-27417 and CP-105,696 on PMN numbers in BALF of Hc-infected mice. Hc-infected mice (i.t., 5 × 105 Hc yeast) were pretreated with SR-27417 (0.1 mg/kg) and/or CP-105,696 (1 mg/kg) orally 2 and 16 hours, respectively, before LTB4 (0.1 μg) injection (in 1 mL PBS) into the air pouch. Vehicle-treated mice received an oral administration of 0.5% CMC or water. BALF was obtained 2 days after Hc infection and PMN numbers determined as described in Materials and Methods. Data are the mean ± SEM of n = 6–12. †P < 0.05 versus vehicle (LTB4 into air pouch).
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fig3: Effect of SR-27417 and CP-105,696 on PMN numbers in BALF of Hc-infected mice. Hc-infected mice (i.t., 5 × 105 Hc yeast) were pretreated with SR-27417 (0.1 mg/kg) and/or CP-105,696 (1 mg/kg) orally 2 and 16 hours, respectively, before LTB4 (0.1 μg) injection (in 1 mL PBS) into the air pouch. Vehicle-treated mice received an oral administration of 0.5% CMC or water. BALF was obtained 2 days after Hc infection and PMN numbers determined as described in Materials and Methods. Data are the mean ± SEM of n = 6–12. †P < 0.05 versus vehicle (LTB4 into air pouch).

Mentions: We next investigated whether a systemic treatment with the anti-inflammatory drugs, CP-105,696 and SR-27417, would interfere with PMN recruitment in the BALF of Hc-infected mice. Our results show that only a concomitant administration of CP-105,696 and SR-27417 significantly decreased PMN numbers by 72% (P < 0.05) in the BALF of Hc-infected mice (Figure 3).


Impairment of neutrophil migration to remote inflammatory site during lung histoplasmosis.

Medeiros AI, Secatto A, Bélanger C, Sorgi CA, Borgeat P, Marleau S, Faccioli LH - Biomed Res Int (2015)

Effect of SR-27417 and CP-105,696 on PMN numbers in BALF of Hc-infected mice. Hc-infected mice (i.t., 5 × 105 Hc yeast) were pretreated with SR-27417 (0.1 mg/kg) and/or CP-105,696 (1 mg/kg) orally 2 and 16 hours, respectively, before LTB4 (0.1 μg) injection (in 1 mL PBS) into the air pouch. Vehicle-treated mice received an oral administration of 0.5% CMC or water. BALF was obtained 2 days after Hc infection and PMN numbers determined as described in Materials and Methods. Data are the mean ± SEM of n = 6–12. †P < 0.05 versus vehicle (LTB4 into air pouch).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4325970&req=5

fig3: Effect of SR-27417 and CP-105,696 on PMN numbers in BALF of Hc-infected mice. Hc-infected mice (i.t., 5 × 105 Hc yeast) were pretreated with SR-27417 (0.1 mg/kg) and/or CP-105,696 (1 mg/kg) orally 2 and 16 hours, respectively, before LTB4 (0.1 μg) injection (in 1 mL PBS) into the air pouch. Vehicle-treated mice received an oral administration of 0.5% CMC or water. BALF was obtained 2 days after Hc infection and PMN numbers determined as described in Materials and Methods. Data are the mean ± SEM of n = 6–12. †P < 0.05 versus vehicle (LTB4 into air pouch).
Mentions: We next investigated whether a systemic treatment with the anti-inflammatory drugs, CP-105,696 and SR-27417, would interfere with PMN recruitment in the BALF of Hc-infected mice. Our results show that only a concomitant administration of CP-105,696 and SR-27417 significantly decreased PMN numbers by 72% (P < 0.05) in the BALF of Hc-infected mice (Figure 3).

Bottom Line: Our results show that pulmonary Hc infection impairs LTB4- or PAF-stimulated PMN recruitment to air pouch.Yet, remote inflammation did not modify PMN numbers in the bronchoalveolar lavage fluid (BALF) of Hc-infected mice.Along that line, our results show that PAF-elicited PMN chemotaxis was abrogated in 5-lipoxygenase-deficient animals.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Sciences, UNESP, 14801-902 Araraquara, SP, Brazil.

ABSTRACT
Histoplasma capsulatum (Hc) induces a pulmonary disease in which leukotrienes promote activation and recruitment of effectors cells. It is also well-recognized that leukotriene B4 (LTB4) and platelet-activating factor (PAF) induce leukocyte recruitment to inflammatory sites. We investigated the impact of pulmonary Hc infection on PMN migration to a remote inflammatory site. Our results show that pulmonary Hc infection impairs LTB4- or PAF-stimulated PMN recruitment to air pouch. Yet, remote inflammation did not modify PMN numbers in the bronchoalveolar lavage fluid (BALF) of Hc-infected mice. Interestingly, the concomitant administration of PAF and LTB4 receptor antagonists inhibited PMN recruitment to both BALF and the remote site, demonstrating cooperation between both mediators. Along that line, our results show that PAF-elicited PMN chemotaxis was abrogated in 5-lipoxygenase-deficient animals. These results suggest caution in the indiscriminate use of anti-inflammatory drugs during infectious diseases.

Show MeSH
Related in: MedlinePlus