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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

Hc lung infection impairs neutrophils recruitment to the remote air pouch. (a and c) LTB4 (0.1 μg) or (b and d) PAF (1 μg) were injected in 1 mL PBS, 2 days after Hc infection in C57Bl/6 mice (i.t., 5 × 105 Hc yeast) (Hc-infected) or PBS (i.t., 100 μL) (noninfected). PBS was injected in air pouch as control (n = 3). Four hours after agonist inoculation in air pouch mice were killed and the cells in (a, b) air pouch and in (c, d) BALF were obtained and PMN in both compartments were counted as described in Materials and Methods. Data are the mean ± SEM of n = 4–8 (a and b) or n = 4–6 (c and d) *P < 0.05 versus PBS; #P < 0.05 noninfected versus Hc-infected mice.
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fig1: Hc lung infection impairs neutrophils recruitment to the remote air pouch. (a and c) LTB4 (0.1 μg) or (b and d) PAF (1 μg) were injected in 1 mL PBS, 2 days after Hc infection in C57Bl/6 mice (i.t., 5 × 105 Hc yeast) (Hc-infected) or PBS (i.t., 100 μL) (noninfected). PBS was injected in air pouch as control (n = 3). Four hours after agonist inoculation in air pouch mice were killed and the cells in (a, b) air pouch and in (c, d) BALF were obtained and PMN in both compartments were counted as described in Materials and Methods. Data are the mean ± SEM of n = 4–8 (a and b) or n = 4–6 (c and d) *P < 0.05 versus PBS; #P < 0.05 noninfected versus Hc-infected mice.

Mentions: In a first series of study, we assessed PMN recruitment to a remote site of inflammation in mice harboring concomitant pulmonary Hc infection. As shown in Figures 1(a) and 1(b), administration of soluble agonist, such as LTB4 or PAF into the air pouch cavity, elicited an intense inflammatory cell infiltrate consisting primarily of PMN into the air pouch of noninfected mice when compared to vehicle inoculation. In contrast, LTB4- or PAF-elicited PMN recruitment to the air pouch was greatly hindered in Hc-infected mice versus uninfected mice, when comparing match given stimuli. As expected, intratracheal inoculation with Hc led to significant PMN accumulation into the BALF of Hc-infected mice (Figures 1(c) and 1(d)). Yet, whether or not LTB4 (Figure 1(c)) or PAF (Figure 1(d)) was injected locally into the air pouch cavity to induce an acute secondary inflammatory response, PMN were still efficiently recruited to the infected lungs (Figures 1(c) and 1(d)). These observations were not attributable to changes in circulating cell numbers inasmuch as no significant differences in PMN blood cells were found between groups 48 h after Hc inoculation (data not shown).


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)

Hc lung infection impairs neutrophils recruitment to the remote air pouch. (a and c) LTB4 (0.1 μg) or (b and d) PAF (1 μg) were injected in 1 mL PBS, 2 days after Hc infection in C57Bl/6 mice (i.t., 5 × 105 Hc yeast) (Hc-infected) or PBS (i.t., 100 μL) (noninfected). PBS was injected in air pouch as control (n = 3). Four hours after agonist inoculation in air pouch mice were killed and the cells in (a, b) air pouch and in (c, d) BALF were obtained and PMN in both compartments were counted as described in Materials and Methods. Data are the mean ± SEM of n = 4–8 (a and b) or n = 4–6 (c and d) *P < 0.05 versus PBS; #P < 0.05 noninfected versus Hc-infected mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4325970&req=5

fig1: Hc lung infection impairs neutrophils recruitment to the remote air pouch. (a and c) LTB4 (0.1 μg) or (b and d) PAF (1 μg) were injected in 1 mL PBS, 2 days after Hc infection in C57Bl/6 mice (i.t., 5 × 105 Hc yeast) (Hc-infected) or PBS (i.t., 100 μL) (noninfected). PBS was injected in air pouch as control (n = 3). Four hours after agonist inoculation in air pouch mice were killed and the cells in (a, b) air pouch and in (c, d) BALF were obtained and PMN in both compartments were counted as described in Materials and Methods. Data are the mean ± SEM of n = 4–8 (a and b) or n = 4–6 (c and d) *P < 0.05 versus PBS; #P < 0.05 noninfected versus Hc-infected mice.
Mentions: In a first series of study, we assessed PMN recruitment to a remote site of inflammation in mice harboring concomitant pulmonary Hc infection. As shown in Figures 1(a) and 1(b), administration of soluble agonist, such as LTB4 or PAF into the air pouch cavity, elicited an intense inflammatory cell infiltrate consisting primarily of PMN into the air pouch of noninfected mice when compared to vehicle inoculation. In contrast, LTB4- or PAF-elicited PMN recruitment to the air pouch was greatly hindered in Hc-infected mice versus uninfected mice, when comparing match given stimuli. As expected, intratracheal inoculation with Hc led to significant PMN accumulation into the BALF of Hc-infected mice (Figures 1(c) and 1(d)). Yet, whether or not LTB4 (Figure 1(c)) or PAF (Figure 1(d)) was injected locally into the air pouch cavity to induce an acute secondary inflammatory response, PMN were still efficiently recruited to the infected lungs (Figures 1(c) and 1(d)). These observations were not attributable to changes in circulating cell numbers inasmuch as no significant differences in PMN blood cells were found between groups 48 h after Hc inoculation (data not shown).

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