There is growing evidence that cytokines such as tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, IL-6, bone morphogenetic proteins (BMP), and nitric oxide (NO) play an important role in the pathogenesis of bone tunnel enlargement following anterior cruciate ligament (ACL) reconstruction. Furthermore, the release of these mediators has been considered a possible reason for the higher incidence of bone tunnel enlargement following hamstring tendon (HST) than following patellar tendon (PT) ACL reconstruction observed in several studies. In this investigation synovial fluid samples from 13 patients were collected immediately before (24+/-7 days after ACL rupture) and 7 days after ACL surgery and values of TNF-alpha, IL-1beta, IL-6, NO, and BMP-2 were analyzed. Furthermore, the incidence of bone tunnel enlargement was assessed using radiographs 38+/-7 weeks after surgery. Six patients underwent autologous HST ACL reconstruction, and in seven patients an PT autograft was used. In the overall patient population there were significantly higher synovial fluid concentrations of IL-6 and BMP-2 postoperatively than preoperatively; TNF-alpha showed a trend towards lower postoperative levels while IL-1beta and NO remained unchanged. The concentrations of NO, TNF-alpha, and IL-6 found in the present study were clearly higher than normal values given in the literature. Assessment of bone tunnel enlargement revealed an average increase in tibial tunnel width of 28.4+/-3.1% with comparable values for HST and PT ACL reconstructions. There was no significant correlation between bone tunnel enlargement and postoperative synovial fluid concentrations of TNF-alpha, IL-1beta, IL-6, NO, and BMP-2. However, all patients with bone tunnel enlargement had higher postoperative concentrations of TNF-alpha, IL-6, and NO in the synovial fluid. There were no significant differences in concentrations between HST and PT groups. In conclusion, we observed an association between tibial bone tunnel enlargement and elevated synovial fluid concentrations of IL-6, TNF-alpha, and NO 7 days after ACL surgery indicating the potential involvement of these biological mediators in the pathogenesis of bone tunnel enlargement. However, there was no difference between HST and PT ACL reconstructions regarding synovial fluid contents of IL-6, TNF-alpha, IL-1beta, NO, and BMP-2, suggesting a comparable biological response between these autografts following their use in ACL reconstruction.
Alveolar macrophages (AM) play a critical role in the removal of inhaled particles or fibers from the lung. Species differences in AM size may affect the number and size range of particles/fibers that can be actually phagocytized and cleared by AM. The purpose of this study was to compare the cell size of rat, hamster, monkey, and human AM by selective flow cytometric analysis of cell volume. Resident AM from CD rats, Syrian golden hamsters, cynomolgus monkeys, and nonsmoking, healthy human volunteers were harvested by standard bronchoalveolar lavage procedures. Morphometric analysis of AM was performed using a flow cytometer that generates volume signals based on the Coulter-type measurement of electrical resistance. We found that hamster and rat AM had diameters of 13.6±0.4 pm (n=8) and 13.1 ±0.2 pm (n=12), respectively. Comparatively, the AM from monkeys (15.3 ± 0.5 pm, n = 7) and human volunteers (21.2 ± 0.3 pm, n = 10) were larger than those from rats and hamsters. The AM from humans were significantly larger (p <0.05) than those from all other species studied, corresponding to a 4-fold larger cell volume of human AM (4990 ± 174 pm3) compared to hamster (1328 ± 123 pm3) and rat (1166±42 pm3) AM. In summary, we have found marked species differences in the cell size of AM. We suggest that the number and size range of particles/fibers that can be phagocytized and cleared by AM may differ among species due to inherent or acquired species differences in AM cell size.
Alveolar macrophages (AM) play a critical role in the removal of inhaled particles or fibers from the lung. Species differences in AM size may affect the number and size range of particles/fibers that can be actually phagocytized and cleared by AM. The purpose of this study was to compare the cell size of rat, hamster, monkey, and human AM by selective flow cytometric analysis of cell volume. Resident AM from CD rats, Syrian golden hamsters, cynomolgus monkeys, and nonsmoking, healthy human volunteers were harvested by standard bronchoalveolar lavage procedures. Morphometric analysis of AM was performed using a flow cytometer that generates volume signals based on the Coulter-type measurement of electrical resistance. We found that hamster and rat AM had diameters of 13.6±0.4 pm (n=8) and 13.1 ±0.2 pm (n=12), respectively. Comparatively, the AM from monkeys (15.3 ± 0.5 pm, n = 7) and human volunteers (21.2 ± 0.3 pm, n = 10) were larger than those from rats and hamsters. The AM from humans were significantly larger (p <0.05) than those from all other species studied, corresponding to a 4-fold larger cell volume of human AM (4990 ± 174 pm3) compared to hamster (1328 ± 123 pm3) and rat (1166±42 pm3) AM. In summary, we have found marked species differences in the cell size of AM. We suggest that the number and size range of particles/fibers that can be phagocytized and cleared by AM may differ among species due to inherent or acquired species differences in AM cell size.
Nitric oxide (NO) is a cellular mediator and regulator of multiple biologic functions. NO released by alveolar macrophages (AM) is suggested to play a role in mediating pulmonary injury. In murine and rat macrophages, the expression of inducible NO synthase (iNOS) and the release of NO are well established. However, the existence of such a pathway in other species remains controversial. In this study, we examined NO production and iNOS expression by AM from rats and hamsters, two laboratory animal species that are characterized by their disparate pulmonary responses to various inhaled irritants/toxicants. AM were treated with lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), or tumor necrosis factor-alpha (TNF-alpha) in vitro, and nitrite, the stable oxidation product of NO, was assayed by the Griess reaction. Rat AM produced NO in a dose- and time-dependent manner upon stimulation with LPS and/or IFN-gamma, but not with TNF-alpha. Surprisingly, hamster AM did not release detectable levels of NO after the same treatment. Although iNOS expression was demonstrated in rat AM by immunocytochemical and Western blot analyses, no induction of iNOS expression could be found in hamster AM. Using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, we found that rat and hamster AM could be induced to express iNOS mRNA after treatment with LPS and IFN-gamma. The results presented here indicate that hamster AM, in contrast to rat AM, lack the ability to express iNOS protein and to generate NO in response to LPS, IFN-gamma, or TNF-alpha in vitro. In conclusion, our data suggest striking differences in iNOS regulation and NO production by AM from rats and hamsters, two rodent species that are commonly used in biomedical research and well-known for their disparate responses to pulmonary irritants/toxicants.
Taken together, our results provide evidence to suggest that iNOS plays a proinflammatory role in acute hyperoxic lung injury.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.