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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

PMN recruitment to air pouch induced by PAF is dependent on endogenous leukotrienes. 5-LO−/− mice were inoculated with PBS or infected with Hc (i.t., 3 × 106 yeast). After 2 days, LTB4 (0.1 μg), PAF (1 μg), or PBS (1 mL) were injected into air pouch, and, 4 h after, PMN were recovered and the counts were determined as described in Materials and Methods. Data are the mean ± SEM of n = 4-5. *P < 0.05 versus vehicle (noninfected mice); #P < 0.05 versus noninfected (LTB4 into air pouch).
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fig4: PMN recruitment to air pouch induced by PAF is dependent on endogenous leukotrienes. 5-LO−/− mice were inoculated with PBS or infected with Hc (i.t., 3 × 106 yeast). After 2 days, LTB4 (0.1 μg), PAF (1 μg), or PBS (1 mL) were injected into air pouch, and, 4 h after, PMN were recovered and the counts were determined as described in Materials and Methods. Data are the mean ± SEM of n = 4-5. *P < 0.05 versus vehicle (noninfected mice); #P < 0.05 versus noninfected (LTB4 into air pouch).

Mentions: The enhanced inhibitory effect of the concomitant administration of CP-105,696 and SR-27417 on soluble agonists-induced PMN recruitment to the remote, localized inflammatory site in both uninfected and Hc-infected mice, suggest a cross-talk between PAF and elicited-endogenous leukotrienes. To corroborate this hypothesis, 5-LO−/− mice were infected (or not) with Hc and air pouches were stimulated with either LTB4 or PAF for 4 h. As shown in Figure 4, exogenous LTB4 induced significant PMN recruitment to the air pouch of uninfected mice. In contrast, Hc infection in 5-LO−/− mice, devoid of endogenous leukotrienes, impaired PMN migration to the air pouch induced by LTB4. However, deficiency of endogenous leukotrienes impaired PMN recruitment into the air pouch induced by PAF in both noninfected and Hc-infected mice, supporting that PAF is critically dependent upon the activation of 5-LO for optimal chemotactic response.


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)

PMN recruitment to air pouch induced by PAF is dependent on endogenous leukotrienes. 5-LO−/− mice were inoculated with PBS or infected with Hc (i.t., 3 × 106 yeast). After 2 days, LTB4 (0.1 μg), PAF (1 μg), or PBS (1 mL) were injected into air pouch, and, 4 h after, PMN were recovered and the counts were determined as described in Materials and Methods. Data are the mean ± SEM of n = 4-5. *P < 0.05 versus vehicle (noninfected mice); #P < 0.05 versus noninfected (LTB4 into air pouch).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: PMN recruitment to air pouch induced by PAF is dependent on endogenous leukotrienes. 5-LO−/− mice were inoculated with PBS or infected with Hc (i.t., 3 × 106 yeast). After 2 days, LTB4 (0.1 μg), PAF (1 μg), or PBS (1 mL) were injected into air pouch, and, 4 h after, PMN were recovered and the counts were determined as described in Materials and Methods. Data are the mean ± SEM of n = 4-5. *P < 0.05 versus vehicle (noninfected mice); #P < 0.05 versus noninfected (LTB4 into air pouch).
Mentions: The enhanced inhibitory effect of the concomitant administration of CP-105,696 and SR-27417 on soluble agonists-induced PMN recruitment to the remote, localized inflammatory site in both uninfected and Hc-infected mice, suggest a cross-talk between PAF and elicited-endogenous leukotrienes. To corroborate this hypothesis, 5-LO−/− mice were infected (or not) with Hc and air pouches were stimulated with either LTB4 or PAF for 4 h. As shown in Figure 4, exogenous LTB4 induced significant PMN recruitment to the air pouch of uninfected mice. In contrast, Hc infection in 5-LO−/− mice, devoid of endogenous leukotrienes, impaired PMN migration to the air pouch induced by LTB4. However, deficiency of endogenous leukotrienes impaired PMN recruitment into the air pouch induced by PAF in both noninfected and Hc-infected mice, supporting that PAF is critically dependent upon the activation of 5-LO for optimal chemotactic response.

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