scholarly journals PGE2 accounts for bidirectional changes in alveolar macrophage self-renewal with aging and smoking

2020 ◽  
Vol 3 (11) ◽  
pp. e202000800
Author(s):  
Loka R Penke ◽  
Jennifer M Speth ◽  
Christina Draijer ◽  
Zbigniew Zaslona ◽  
Judy Chen ◽  
...  

Alveolar macrophages (AMs) are resident immune cells of the lung that are critical for host defense. AMs are capable of proliferative renewal, yet their numbers are known to decrease with aging and increase with cigarette smoking. The mechanism by which AM proliferation is physiologically restrained, and whether dysregulation of this brake contributes to altered AM numbers in pathologic circumstances, however, remains unknown. Mice of advanced age exhibited diminished basal AM numbers and contained elevated PGE2 levels in their bronchoalveolar lavage fluid (BALF) as compared with young mice. Exogenous PGE2 inhibited AM proliferation in an E prostanoid receptor 2 (EP2)-cyclic AMP-dependent manner. Furthermore, EP2 knockout (EP2 KO) mice exhibited elevated basal AM numbers, and their AMs resisted the ability of PGE2 and aged BALF to inhibit proliferation. In contrast, increased numbers of AMs in mice exposed to cigarette smoking were associated with reduced PGE2 levels in BALF and were further exaggerated in EP2 KO mice. Collectively, our findings demonstrate that PGE2 functions as a tunable brake on AM numbers under physiologic and pathophysiological conditions.

1997 ◽  
Vol 272 (6) ◽  
pp. L1066-L1069
Author(s):  
H. Kanazawa ◽  
H. Kamoi ◽  
T. Kawaguchi ◽  
S. Shoji ◽  
T. Fujii ◽  
...  

Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.


1993 ◽  
Vol 147 (6_pt_1) ◽  
pp. 1562-1568 ◽  
Author(s):  
Hideki Takahashi ◽  
Kazumi Ishidoh ◽  
Daisuke Muno ◽  
Akihiko Ohwada ◽  
Toshihiro Nukiwa ◽  
...  

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lyné van Rensburg ◽  
Johann M. van Zyl ◽  
Johan Smith ◽  
Pierre Goussard

Abstract Background Bronchoalveolar lavage is a useful bronchoscopy technique. However, studies in “normal” children populations are few. Furthermore, the anti-inflammatory effects of exogenous pulmonary surfactants on the bronchoalveolar cellular components are limited. Methods Thirty children, aged 3 to 14 years, underwent diagnostic bronchoscopy and bronchoalveolar lavage. Differential cytology, cytokine and chemokine measurements were performed on the fluid after exogenous surfactant exposure. The aim of the study was to investigate the potential anti-inflammatory effects of exogenous surfactants on the bronchoalveolar lavage fluid, specifically alveolar macrophages of healthy South African children. Results Alveolar macrophages were the predominant cellular population in normal children. Patients with inflammatory pneumonopathies had significantly more neutrophils. Levels of inflammatory cytokines were significantly lower after exogenous surfactant exposure. Moreover, IL-10 and IL-12 cytokine secretion increased after exogenous surfactant exposure. Conclusion This study provides the first data on bronchoalveolar lavage of healthy South African children. Bronchoalveolar lavage fluid from patients with pulmonary inflammation was characterised by neutrophilia. Finally, we propose that exogenous surfactant treatment could help alleviate inflammation in diseased states where it occurs in the tracheobronchial tree.


2013 ◽  
Vol 74 (7) ◽  
pp. 858-860 ◽  
Author(s):  
Joanna Domagala-Kulawik ◽  
Tomasz Urbankowski ◽  
Aleksandra Safianowska

2004 ◽  
Vol 11 (4) ◽  
pp. 795-798 ◽  
Author(s):  
E. C. Soethout ◽  
K. E. Müller ◽  
A. J. M. van den Belt ◽  
V. P. M. G. Rutten

ABSTRACT A method is proposed to identify leukocyte subpopulations in bovine bronchoalveolar lavage fluid by dual-laser flow cytometry. The technique uses several parameters, i.e., exclusion of highly autofluorescent alveolar macrophages and inclusion of leukocytes on the basis of labeling by specific antibodies and light scatter characteristics.


1998 ◽  
Vol 47 (2) ◽  
pp. 109-116
Author(s):  
Risa Nakahara ◽  
Shuhei Takemura ◽  
Hideki Onodera ◽  
Yoshihiro Kasamatsu ◽  
Nobuyuki Seto ◽  
...  

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