We showed recently that mononuclear phagocyte system (MPS) cells provide a buffering mechanism for salt-sensitive hypertension by driving interstitial lymphangiogenesis, modulating interstitial Na(+) clearance, and increasing endothelial NO synthase protein expression in response to very high dietary salt via a tonicity-responsive enhancer binding protein/vascular endothelial growth factor C regulatory mechanism. We now tested whether isotonic saline and deoxycorticosterone acetate (DOCA)-salt treatment leads to a similar regulatory response in Sprague-Dawley rats. Male rats were fed a low-salt diet and received tap water (low-salt diet LSD), 1.0% saline (high-salt diet HSD), or DOCA+1.0% saline (DOCA-HSD). To test the regulatory role of interstitial MPS cells, we further depleted MPS cells with clodronate liposomes. HSD and DOCA-HSD led to Na(+) accumulation in the skin, MPS-driven tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated hyperplasia of interstitial lymph capillaries, and increased endothelial NO synthase protein expression in skin interstitium. Clodronate liposome MPS cell depletion blocked MPS infiltration in the skin interstitium, resulting in unchanged tonicity-responsive enhance binding protein/vascular endothelial growth factor C levels and absent hyperplasia of the lymph capillary network. Moreover, no increased skin endothelial NO synthase protein expression occurred in either clodronate liposome-treated HSD or DOCA-salt rats. Thus, absence of the MPS-cell regulatory response converted a salt-resistant blood-pressure state to a salt-sensitive state in HSD rats. Furthermore, salt-sensitive hypertension in DOCA-salt rats was aggravated. We conclude that MPS cells act as onsite controllers of interstitial volume and blood pressure homeostasis, providing a local regulatory salt-sensitive tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated mechanism in the skin to maintain normal blood pressure in states of interstitial Na(+) and Cl(-) accumulation. Failure of this physiological extrarenal regulatory mechanism leads to a salt-sensitive blood pressure response.
- MeSH
- chlorid sodný farmakologie MeSH
- deoxykortikosteron farmakologie MeSH
- dichlormethylendifosfonát farmakologie MeSH
- exprese genu fyziologie MeSH
- fagocyty cytologie fyziologie MeSH
- financování organizované MeSH
- hypertenze metabolismus patofyziologie MeSH
- krevní tlak fyziologie MeSH
- krysa rodu rattus MeSH
- kuchyňská sůl farmakokinetika MeSH
- kůže metabolismus MeSH
- lymfangiogeneze fyziologie MeSH
- lymfatické cévy cytologie fyziologie MeSH
- mineralokortikoidy farmakologie MeSH
- potkani Sprague-Dawley MeSH
- proteinurie metabolismus patofyziologie MeSH
- synthasa oxidu dusnatého, typ III metabolismus MeSH
- TNF-alfa genetika metabolismus MeSH
- transkripční faktory genetika metabolismus MeSH
- vaskulární endoteliální růstový faktor C genetika metabolismus MeSH
- vodní a elektrolytová rovnováha fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Mononuclear phagocytes (MP) are cells of nonspecific immunity, playing an essential role in defense against bacterial pathogens. Although various MP subpopulations have been described in the pig, relations among these populations in vivo are unknown to date. The present study was aimed at describing porcine MP subpopulations infiltrating inflamed tissue of pigs under in vivo conditions. Actinobacillus pleuropneumoniae (APP) infection was used to induce an inflammatory response. CD172alpha, CD14, CD163, MHCII and CD203alpha cell surface molecules were used to identify MP by flow cytometry. Changes in MP subpopulations in the peripheral blood (PB) and bone marrow (BM) compartments along with the analysis of MP appearing in the inflamed lungs were assessed to elucidate the possible origin and maturation stages of the infiltrating MP. The MP population migrating to the inflamed lungs was phenotype CD14+ CD163+ CD203alpha+/- MHCII+/-. Concomitantly, after APP infection there was an increase in the PB MP CD14+ CD163+ CD203alpha- MHC II- population, suggesting that these cells give rise to inflammatory monocytes/macrophages. The CD203alpha and MHCII molecules appear on these cells after leaving the PB. In healthy animals, the BM MP precursors were represented by CD14- CD163- cells maturing directly into CD14+ CD163- that were then released into the PB. After infection, an altered maturation pathway of MP precursors appeared, represented by CD14- CD163- CD203alpha- MHCII- MP directly switching into CD14+ CD163+ CD203alpha- MHCII- MP. In conclusion, two different MP maturation pathways were suggested in pigs. The use of these pathways differs under inflammatory and noninflammatory conditions.
- MeSH
- Actinobacillus pleuropneumoniae MeSH
- buňky kostní dřeně fyziologie MeSH
- CD antigeny genetika metabolismus MeSH
- fagocyty cytologie fyziologie MeSH
- geny MHC třídy II genetika fyziologie MeSH
- infekce bakteriemi rodu Actinobacillus krev mikrobiologie patologie veterinární MeSH
- nemoci prasat mikrobiologie patologie MeSH
- plíce cytologie MeSH
- prasata MeSH
- regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- Candida albicans cytologie metabolismus MeSH
- fagocytóza MeSH
- fagocyty cytologie MeSH
- glykoproteiny chemie metabolismus MeSH
- lektiny metabolismus MeSH
- lidé MeSH
- methakryláty metabolismus MeSH
- sacharidové sekvence MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- arteriae mesentericae zranění MeSH
- cytologické techniky metody využití MeSH
- fagocyty * cytologie fyziologie patologie MeSH
- krysa rodu rattus MeSH
- luminiscence diagnostické užití MeSH
- mezenteriální cévní okluze MeSH
- modely nemocí na zvířatech MeSH
- peroxidasa izolace a purifikace MeSH
- reaktivní formy kyslíku MeSH
- reperfuzní poškození * MeSH
- statistika jako téma MeSH
- tenké střevo * fyziologie patologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- bronchoskopie metody přístrojové vybavení MeSH
- diferenciální diagnóza metody MeSH
- dítě MeSH
- eozinofily cytologie MeSH
- fagocyty cytologie MeSH
- léčebná irigace metody MeSH
- leukocyty cytologie MeSH
- lidé MeSH
- plicní nemoci diagnóza MeSH
- předškolní dítě MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- předškolní dítě MeSH