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Macrophage Response (macrophage + response)
Selected AbstractsThe contribution of activated phagocytes and myelin degeneration to axonal retraction/dieback following spinal cord injuryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2004Lowell T. McPhail Abstract Myelin-derived molecules inhibit axonal regeneration in the CNS. The Long,Evans Shaker rat is a naturally occurring dysmyelinated mutant, which although able to express the components of myelin lacks functional myelin in adulthood. Given that myelin breakdown exposes axons to molecules that are inhibitory to regeneration, we sought to determine whether injured dorsal column axons in a Shaker rat would exhibit a regenerative response absent in normally myelinated Long,Evans (control) rats. Although Shaker rat axons did not regenerate beyond the lesion, they remained at the caudal end of the crush site. Control rat axons, in contrast, retracted and died back from the edge of the crush. The absence of retraction/dieback in Shaker rats was associated with a reduced phagocytic reaction to dorsal column crush around the caudal edge of the lesion. Systemic injection of minocycline, a tetracycline derivative, in control rats reduced both the macrophage response and axonal retraction/dieback following dorsal column injury. In contrast, increasing macrophage activation by spinal injection of the yeast particulate zymosan had no effect on axonal retraction/dieback in Shaker rats. Schwann cell invasion was reduced in minocycline-treated control rats compared with untreated control rats, and was almost undetectable in Shaker rats, suggesting that like axonal retraction/dieback, spinal Schwann cell infiltration is dependent upon macrophage-mediated myelin degeneration. These results indicate that following spinal cord injury the phagocyte-mediated degeneration of myelin and subsequent exposure of inhibitory molecules to the injured axons contributes to their retraction/dieback. [source] Wear particle analysis of highly crosslinked polyethylene isolated from a failed total hip arthroplastyJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2008Yukihide Minoda Abstract Polyethylene wear particles are one of the most important factors affecting the results of total hip arthroplasty (THA). To reduce wear generation and to achieve better long-term results of THA, highly crosslinked polyethylene (HXPE) has recently been introduced and come into wide use. Thus far, however, there have been no reports on in vivo analysis of HXPE wear particles. We isolated HXPE wear particles from periprosthetic tissue of a failed THA and analyzed using scanning electron microscope. The number of particles was 5.33 × 107 g,1. Particle size (equivalent circle diameter) was 0.66 ± 0.40 ,m (mean ± standard error). Aspect ratio and roundness were 1.37 ± 0.26 and 1.44 ± 0.67, respectively. All the particles were round shaped, and "fibrils" or "shreds" were not detected. Thus far, this was the first report on in vivo wear particle analysis of HXPE. HXPE generated less, smaller, and rounder particles, compared with the corresponding reported values for particles generated from conventional polyethylene. These characteristics might affect macrophage response, osteolysis, and long-term results of THA with HXPE. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008 [source] Healing process induced by three composite prostheses in the repair of abdominal wall defectsJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2002Juan M. Bellón Abstract The present study compared the performance of three composite prostheses used to repair abdominal wall defects in rabbits. Two of them [Parietex Composite® (PC) and Composix® (CS)] are commonly used in clinical practice and one was designed by the present team (PL-PU99). At 14 and 90 days postimplant, specimens were obtained for morphological, macrophage response (RAM-11) and morphometric and biomechanical analysis. The prosthetic area covered by adhesions was significantly greater (p < 0.05) in the CS group (6.83 ± 2.31 cm2) than in PC (0.11 ± 0.02 cm2) or PL-PU99 (0.10 ± 0.07 cm2). At 14 days, it was observed a homogeneous, organized, well-vascularized neoperitoneum that was significantly thicker (p < 0.05) in PL-PU99. Except in the CS implants, this layer was covered by a continuous mesothelium. All three composites achieved good recipient tissue integration. Highest macrophage levels were recorded at 14 days with significantly higher values in the PL-PU99 prosthesis. Biomechanical strength was significantly greater (p < 0.05) in CS at two weeks postimplant, but it was similar at 90 days. These findings suggest that the three composites show ideal integration with host tissue, along with similar biomechanical strength at 90 days, and significantly higher adhesion formation is induced by the CS prosthesis, possibly due to incomplete mesothelialization of the lower prosthetic surface. © 2002 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 63: 182,190, 2002; DOI 10.002/jbm.10123 [source] Upregulation of intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 after unilateral nerve injury in the peripheral taste systemJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2007Melissa Ann Cavallin Abstract In the peripheral taste system, activated macrophages are recruited to both sides of the tongue after unilateral sectioning of the chorda tympani nerve (CT). Neural degeneration elicits macrophage entry in other systems by upregulating vascular adhesion molecules. We hypothesized that CT sectioning leads to a bilateral increase in intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression on lingual vessels. To test this hypothesis, rats were euthanized at time points from 6 hr to 7 days post-sectioning. Frozen sections of tongue were processed for immunohistochemical staining for ICAM-1 and VCAM-1. Tongue homogenates from additional rats were analyzed with ELISA. ICAM-1 expression increases first on the denervated side of the tongue at 24 hr post-section and then on the uninjured side at 48 hr post-section. ICAM-1 remains elevated through Day 7 post-sectioning on both sides of the tongue. Dietary sodium restriction, which prevents the macrophage response to nerve sectioning, had no effect on ICAM-1 levels. VCAM-1+ vessels are increased on the denervated side of the tongue at 24,48 hr post-section in control-fed rats. However, dietary sodium restriction prevents the increase. These results indicate that vascular adhesion molecules are differentially regulated by CT sectioning. We suggest that macrophage entry, migration, and modulation of taste function are downstream of dynamic expression of adhesion molecules. © 2006 Wiley-Liss, Inc. [source] Differential apoptotic response of J774 macrophages to alumina and ultra-high-molecular-weight polyethylene particlesJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2002Alain Petit We recently identified apoptosis in in vitro wear particle-stimulated macrophages. The recent explosion of interest in apoptosis lies in the fact that it is under positive and negative regulation through evolutionary conserved biochemical pathways. It may also be possible to modulate macrophage apoptosis in the treatment of periprosthetic osteolysis. The purpose of this study was to compare the macrophage response to identically sized particles of alumina ceramic (Al2O3) and ultra-high-molecular-weight polyethylene (UHMWPE) in terms of TNF-, release and induction of apoptosis. J774 mouse macrophages were incubated for 0,24 h in the presence of Al2O3 and UHMWPE particles. TNF-, release was measured by ELISA; Poly(ADP-ribose)polymerase (PARP) and caspase-3 expression was analyzed by Western blot; DNA fragmentation (DNA laddering) was visualized on agarose gel containing ethidium bromide. Al2O3 particles induced TNF-, release after 4 h incubation with concentrations reaching 483 and 800 pg/ml after 24 h with 125 and 250 particles/macrophage, respectively (control = 161 pg/ml) (P < 0.05 vs. control). The same concentrations of UHMWPE particles induced a much larger and significant TNF-, release after only 1 h incubation, increasing up to 6250 pg/ml after 24 h (P < 0.05 vs. control). Western blot analysis demonstrated that the active caspase-3 fragment (17 kDa) and the proteolytic PARP fragment (85 kDa) were expressed after 2 h incubation with 125 and 250 Al2O3 particles/macrophage. The active caspase-3 and the PARP fragment had lower expression and appeared after a longer incubation time (8 h) with 125 and 250 UHMWPE particles/macrophage. Finally, DNA fragmentation (DNA laddering) was observed after 16 h with 125 and 250 particles of Al2O3 per macrophage whereas no laddering was induced by UHMWPE particles even after 24 h incubation. This study shows that although both Al2O3 and UHMWPE particles induce TNF-, release, this stimulation was much greater (8,10 times higher) with UHMWPE than A12O3 (P < 0.05 vs. control). As well, the induction of apoptosis, as measured by activation of caspase-3, PARP cleavage and DNA laddering, is different for these two particles, being faster and more important with Al2O3 than UHMWPE. We hypothesize that the ability of Al2O3 to induce macrophage apoptosis may explain the lower TNF-, release observed with these particles and explain the differences seen in osteolysis patterns of ceramic,ceramic (CC) vs. metal,polyethylene (Mpe) articulations. In conclusion, apoptosis may be a major internal mechanism to decrease macrophage activity and may be a desired therapeutic endpoint. The identification of an apoptosis-related pathway in the macrophage response to ceramic particles provides crucial data for a rational approach in the treatment and/or prevention of periprosthetic osteolysis. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Scavenger receptor A is expressed by macrophages in response to Porphyromonas gingivalis, and participates in TNF-, expressionMOLECULAR ORAL MICROBIOLOGY, Issue 6 2009M. T. Baer Introduction:,Porphyromonas gingivalis is a periodontopathic bacterium closely associated with generalized aggressive periodontal disease. Pattern recognition receptors (PRRs) participate in host response to this organism. It is likely that PRRs not previously recognized as part of the host response to P. gingivalis also participate in host response to this organism. Methods and Results:, Employing qRT-PCR, we observed increased msr1 gene expression at 2, 6, and 24 h of culture with P. gingivalis strain 381. Flow cytometry revealed increased surface expression of SR-A protein by the 24 h time point. Macrophages cultured with an attachment impaired P. gingivalis fimA - mutant (DPG3) expressed intermediate levels of SR-A expression. Heat-killed P. gingivalis stimulated SR-A expression similar to live bacteria, and purified P. gingivalis capsular polysaccharide stimulated macrophage SR-A expression, indicating that live whole organisms are not necessary for SR-A protein expression in macrophage response. As SR-A is known to play a role in lipid uptake by macrophages, we tested the ability of low-density lipoprotein (LDL) to influence the SR-A response of macrophages to P. gingivalis, and observed no effect of LDL on P. gingivalis -elicited SR-A expression. Lastly, we observed that SR-A knockout (SR-A,/,) mouse macrophages produced significantly more tumor necrosis factor (TNF)-, than wild type mouse macrophages cultured with P. gingivalis. Conclusion:, These data identify that SR-A is expressed by macrophages in response to P. gingivalis, and support that this molecule plays a role in TNF-, production by macrophages to this organism. [source] NTPDase1 governs P2X7 -dependent functions in murine macrophagesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2010Sébastien A. Lévesque Abstract P2X7 receptor is an adenosine triphosphate (ATP)-gated ion channel within the multiprotein inflammasome complex. Until now, little is known about regulation of P2X7 effector functions in macrophages. In this study, we show that nucleoside triphosphate diphosphohydrolase 1 (NTPDase1)/CD39 is the dominant ectonucleotidase expressed by murine peritoneal macrophages and that it regulates P2X7 -dependent responses in these cells. Macrophages isolated from NTPDase1-null mice (Entpd1,/,) were devoid of all ADPase and most ATPase activities when compared with WT macrophages (Entpd1+/+). Entpd1,/, macrophages exposed to millimolar concentrations of ATP were more susceptible to cell death, released more IL-1, and IL-18 after TLR2 or TLR4 priming, and incorporated the fluorescent dye Yo-Pro-1 more efficiently (suggestive of increased pore formation) than Entpd1+/+ cells. Consistent with these observations, NTPDase1 regulated P2X7 -associated IL-1, release after synthesis, and this process occurred independently of, and prior to, cytokine maturation by caspase-1. NTPDase1 also inhibited IL-1, release in vivo in the air pouch inflammatory model. Exudates of LPS-injected Entpd1,/, mice had significantly higher IL-1, levels when compared with Entpd1+/+ mice. Altogether, our studies suggest that NTPDase1/CD39 plays a key role in the control of P2X7 -dependent macrophage responses. [source] The macrophage and the apoptotic cell: an innate immune interaction viewed simplistically?IMMUNOLOGY, Issue 1 2004Christopher D. Gregory Summary Macrophages play important roles in the clearance of dying and dead cells. Typically, and perhaps simplistically, they are viewed as the professional phagocytes of apoptotic cells. Clearance by macrophages of cells undergoing apoptosis is a non-phlogistic phenomenon which is often associated with actively anti-inflammatory phagocyte responses. By contrast, macrophage responses to necrotic cells, including secondarily necrotic cells derived from uncleared apoptotic cells, are perceived as proinflammatory. Indeed, persistence of apoptotic cells as a result of defective apoptotic-cell clearance has been found to be associated with the pathogenesis of autoimmune disease. Here we review the mechanisms by which macrophages interact with, and respond to, apoptotic cells. We suggest that macrophages are especially important in clearing cells at sites of histologically visible, high-rate apoptosis and that, otherwise, apoptotic cells are removed largely by non-macrophage neighbours. We challenge the view that necrotic cells, including persistent apoptotic cells are, of necessity, proinflammatory and immunostimulatory and suggest that, under appropriate circumstances, persistent apoptotic cells can provide a prolonged anti-inflammatory stimulus. [source] Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2008Panagiotis Koulouvaris Abstract Interactions between periprosthetic cells and prosthetic wear debris have been recognized as an important event in the development of osteolysis and aseptic loosening. Although the ability of wear debris to activate pro-inflammatory macrophage signaling has been documented, the full repertoire of macrophage responses to wear particles has not been established. Here, we examined the involvement of alternative macrophage activation and defective osteogenic signaling in osteolysis. Using real-time RT-PCR analysis of periprosthetic soft tissue from osteolysis patients, we detected elevated levels of expression of alternative macrophage activation markers (CHIT1, CCL18), chemokines (IL8, MIP1 ,) and markers of osteoclast precursor cell differentiation and multinucleation (Cathepsin K, TRAP, DC-STAMP) relative to osteoarthritis controls. The presence of cathepsin K positive multinuclear cells was confirmed by immunohistochemistry. Reduced expression levels of the osteogenic signaling components BMP4 and FGF18 were detected. Expression levels of TNF-,, IL-6, and RANKL were unchanged, while the anti-osteoclastogenic cytokine OPG was reduced in osteolysis patients, resulting in elevated RANKL:OPG ratios. In vitro studies confirmed the role of particulate debris in alternative macrophage activation and inhibition of osteogenic signaling. Taken together, these results suggest involvement in osteolysis of alternative macrophage activation, accompanied by elevated levels of various chemokines. Increased recruitment and maturation of osteoclast precursors is also observed, as is reduced osteogenesis. These findings provide new insights into the molecular pathogenesis of osteolysis, and identify new potential candidate markers for disease progression and therapeutic targeting. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:106,116, 2008 [source] Involvement of complement receptor 3 (CR3) and scavenger receptor in macrophage responses to wear debrisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2006Diptendu S. Rakshit Abstract The ability of prosthetic wear debris to induce pro-inflammatory responses in macrophages is widely appreciated, but little is known about the molecular mechanisms involved in particle recognition. Specifically, the nature of the cell surface receptors that interact with wear debris is poorly understood. Elucidating the identities of these receptors and how they interact with different types of wear debris are critical to understanding how wear debris initiates periprosthetic osteolysis. We examined the involvement of opsonization, complement receptor 3 (CR3), and scavenger receptor A (SRA), in responses to polymethylmethacrylate (PMMA) and titanium wear particles. Serum dependence of pro-inflammatory responses to PMMA and titanium was tested, and serum proteins that adhered to these two types of particles were identified. Several serum proteins, including known opsonins such as C3bi and fibronectin, adhered to PMMA but not titanium, and serum was required for pro-inflammatory signaling induced by PMMA, but not by titanium. Phagocytosis of PMMA and titanium by macrophages was demonstrated by flow cytometry. Blocking CR3 specifically inhibited phagocytosis of PMMA by macrophages, whereas blocking SRA specifically inhibited titanium uptake. Direct involvement of CR3 and SRA in cell,particle interaction was assessed by expression of these receptors in nonphagocytic HEK293 cells. CR3 specifically induced cell binding to PMMA particles and adhesion to PMMA-coated plates, while SRA specifically induced binding to titanium particles and adhesion to titanium-coated plates. Taken together, these results suggest involvement of opsonization, complement, and integrin receptors, including CR3 and fibronectin receptors, in PMMA action, and an involvement of scavenger receptors in responses to titanium. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:2036,2044, 2006 [source] Distinct pattern of microglial response, cyclooxygenase-2, and inducible nitric oxide synthase expression in the aged rat brain after excitotoxic damageJOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2008O. Campuzano Abstract Microglial and inflammatory responses to acute damage in aging are still poorly understood, although the aged brain responds differently to injury, showing poor lesion outcome. In this study, excitotoxicity was induced by intrastriatal injection of N-methyl-D-aspartate in adult (3,4 months) and aged (22,24 months) rats. Cryostat brain sections were processed for the analysis of microglial response by lectin histochemistry and cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) expression by immunohistochemistry and confocal analysis. Aged injured animals showed more widespread area of microglial response at 12 hr postlesion (hpl) and greater microglia/macrophage density at 3 days postlesion (dpl). However, aged reactive microglia showed prevalence of ramified morphologies and fewer amoeboid/round forms. Aged injured animals presented a diminished area of COX2 expression, but a significantly larger density of COX2+ cells, with higher numbers of COX2+ neurons during the first 24 hpl and COX2+ microglia/macrophages later. In contrast, the amount of COX2+ neutrophils was diminished in the aged. iNOS was more rapidly induced in the aged injured striatum, with higher cell density at 12 hpl, when expression was mainly neuronal. From 1 dpl, both the iNOS+ area and the density of iNOS+ cells were reduced in the aged, with lower numbers of iNOS+ neurons, microglia/macrophages, neutrophils, and astrocytes. In conclusion, excitotoxic damage in aging induces a distinct pattern of microglia/macrophage response and expression of inflammatory enzymes, which may account for the changes in lesion outcome in the aged, and highlight the importance of using aged animals for the study of acute age-related insults. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||