An in vitro investigation of telocytes-educated macrophages: morphology, heterocellular junctions, apoptosis and invasion analysis

Abstract

BackgroundTelocytes (TCs), a recently discovered novel type of interstitial cells, were also found in a wide variety of human and mammalian reproductive organs/tissues, including uterus, oviduct and placenta. Previously, we demonstrated that TCs-conditioned media was capable of activating peritoneal macrophages (pMACs) through paracrine effects. This study investigates the hypothesis that direct interaction of TCs with pMACs will also play a significant role in immunoregulation of pMACs.MethodsTCs and pMACs were derived from the uterus and intraperitoneal cavity of female BALB/c mice, respectively. TCs were identified by immunofluorescence and then co-cultured directly with pMACs for 24 h without added cytokines, to observe the in vitro biological behavior of pMACs. We used histochemical staining to study morphology and mitochondrial metabolism of pMACs, scanning electron microscopy to study heterocellular junctions, flow cytometry to investigate mitochondrial membrane potential (ΔΨm) and apoptosis, and transwell chambers to study invasion ability. Student-t test was used accordingly.ResultsPresently, TCs with typical structure and immunophenotype of double CD-34-positive/vimentin-positive were successfully isolated. pMACs co-cultured with TCs showed obviously morphological activation, with enhanced energy metabolism (P < 0.05). Meanwhile, direct physical cell-to-cell interaction promoted the development of heterocellular junctions between TCs and pMACs. Furthermore, TCs treatment markedly reduced the depletion of ΔΨm in co-cultured pMACs (all P < 0.05), and inhibited their apoptosis (P < 0.05). Functionally, pMACs co-cultured with TCs showed enhanced invasion ability (P < 0.05).ConclusionsDirect physical cell-to-cell interaction promoted the development of heterocellular junctions between TCs and pMACs, presumably responsible for the observed novel efficient way of pMACs activation via mitochondrial signaling pathway. TCs-educated pMACs might be a promising way to restore the defective immunosurveillance in endometriosis (EMs), led to the enhanced treatment efficacy of EMs in a simple and clinically feasible fashion.

Morphological and immunohistochemical phenotype of TCs in the intestinal bulb of Grass carp and their potential role in intestinal immunity

“…TCs produce several secretory molecules and factors contributing to the functional significance.Gene analysis 2 and proteomics analysis 3 are investigated for TCs. The functional contributions of TCS are supposed to be related to angiogenesis 4 , and development, maintenance of homeostatic balance 4 , immunosurveillance 5 , tissue regeneration and repair through providing adequate microenvironment for stem cell niche and promoting their differentiation 6 , 7 .…”

Telocytes in the Normal and Pathological Peripheral Nervous System

“…TCs are a heterogenous population [ 4 , 5 ] and express CD34 and PDGFRa, among other markers. Several roles have been hypothesized for TCs in tissue homeostasis, morphogenesis, regeneration and repair, including intercellular communication with the integration of tissue components by cell-to-cell-signalling or extracellular shedding vesicles and paracrine molecules [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ], the control and organisation of the extracellular matrix [ 15 ], the creation of microenvironments within the tissues [ 17 , 18 , 19 ], structural support [ 17 , 20 , 21 , 22 , 23 , 24 , 25 ], endocytosis with the internalization of small particles [ 9 ], the control and regulation of other cell types [ 26 ], guidance to cell migration during development and the contribution of scaffolds [ 14 , 17 , 27 , 28 , 29 , 30 , 31 ], immunomodulation and immunosurveillance [ 27 ], the inhibition of apoptosis (inhibition of oxidative stress and prevention of cellular ageing) [ 26 , 32 ], neurotransmission (e.g., contribution of slow waves generated by interstitial cells of Cajal) [ 10 , 15 , 25 , 33 , 34 , 35 ] and the modulation of stem cells (control of their growth and differentiation) [ 21 , 27 , 36 , 37 ,…”

Telocytes: New Connecting Devices in the Stromal Space of Organs

“…Recently, TCs were found to activate and "educate" peritoneal macrophages (pMACs) with the aid of telopodes by direct physical contact through heterocellular junctions or using a TCs-conditioned media through paracrine mechanisms [85]. This is suggestive for a role in immunosurveillance [85].…”