Post-traumatic Curvularia sp. arthritis in an immunocompetent adult.

A 44-year-old woman, victim of a road accident in Mali was diagnosed with left knee arthritis. Joint effusion aspiration and subcutaneous surgical biopsies were positive for a melanized asexual ascomycete. Using microscopy and molecular biology, the fungus was identified as Curvularia sp. In vitro antifungal susceptibility was determined by the EUCAST broth microdilution reference technique and by E-test. The patient was treated with liposomal amphotericin B before posaconazole relay. Mycological samples obtained 10 days after starting the antifungal therapy by liposomal amphotericin B were negative in culture. Curvularia spp. are environmental fungi which can under certain conditions be pathogenic for humans.

Intra-articular depletion of macrophages increases acute synovitis and alters macrophage polarity in the injured mouse knee.

OBJECTIVE: Acute synovial inflammation following joint trauma is associated with posttraumatic arthritis. Synovial macrophages have been implicated in degenerative changes. In this study, we sought to elucidate the role of intra-articular macrophages in the acute inflammatory response to fracture in the mouse knee. METHOD: A closed articular fracture was induced in two models of synovial macrophage depletion: genetically-modified MaFIA mice administered AP20187 to induce programmed macrophage apoptosis, and wild-type C57BL/6 mice administered clodronate liposomes, both via intra-articular injection. Synovial inflammation, bone morphology, and levels of F4/80+ macrophages, NOS2+ M1 macrophages, and CD206+ M2 macrophages were quantified 7 days after fracture using histology and micro-computed tomography. RESULTS: Intra-articular macrophage depletion with joint injury did not reduce acute synovitis or the number of synovial macrophages 7 days after fracture in either macrophage-depleted MaFIA mice or in clodronate-treated C57BL/6 mice. In macrophage-depleted MaFIA mice, macrophage polarity shifted to a dominance of M1 macrophages and a reduction of M2 macrophages in the synovial stroma, indicating a shift in M1/M2 macrophage ratio in the joint following injury. Interestingly, MaFIA mice depleted 2 days prior to fracture demonstrated increased synovitis (P = 0.003), reduced bone mineral density (P = 0.0004), higher levels of M1 macrophages (P = 0.013), and lower levels of M2 macrophages (not statistically significant, P=0.084) compared to control-treated MaFIA mice. CONCLUSION: Our findings indicate that macrophages play a critical immunomodulatory role in the acute inflammatory response surrounding joint injury and suggest that inhibition of macrophage function can have prominent effects on joint inflammation and bone homeostasis after joint trauma.

Cactus Spine Wounds: A Case Report and Short Review of the Literature.

INTRODUCTION: Cactus plants are commonly seen in arid southwestern regions of the United States. Due to their ready availability, they have become a popular houseplant. The spines or glochidia can easily puncture the skin with only minor pressure (ie, bumping or touching the cactus). Removal of the offending spine is difficult, even with tweezers. CASE: An 18-year-old woman initially self-removed the spines, and marked discomfort and intense erythematous reaction developed within 8 to 10 hours. Patient presented to the emergency room at Mercy Hospital and Trauma Center (Janesville, Wisconsin), where spine removal was unsuccessful. RESULTS: Following emergency room discharge, she had difficulty walking from pain and swelling and was advised to use heat packs, take amoxicillin/clavulanic acid, and rest with her leg elevated for another 7 days along with using eye drops for eye irritation. The lesions slowly improved over the next several months. CONCLUSION: The case of multiple barrel cactus spine injuries with severe pain and swelling is presented herein as well as a review of the treatment options and complications of cactus spine injuries.

Comparison of Synovial Fluid Cytokine Levels between Traumatic Knee Injury and End-Stage Osteoarthritis.

Degenerative osteoarthritis (OA) has been associated with elevated synovial fluid cytokines. It is unclear whether traumatic knee injuries are a trigger to the chemical process that leads to OA. The purpose of this study was to compare the synovial fluid cytokine levels between knees undergoing arthroscopy due to a documented inciting injury and knees undergoing primary arthroplasty due to end-stage OA without a previous inciting injury. Synovial fluid samples were prospectively collected from knees undergoing arthroscopic surgeries due to ligamentous or meniscal knee injuries (knee injury group, n = 16) and primary arthroplasty due to OA (end-stage OA group, n = 14). In the knee injury group, patients had none or minimal OA and at least 30 days from the inciting injury. Exclusion criteria for both groups included inflammatory arthropathy (n = 1) and insufficient fluid for analysis (n = 1). In addition to synovial fluid cytokines, preoperative demographic, clinical, and functional data (Knee Injury and Osteoarthritis Outcome Score [KOOS]) were collected and compared between the groups. The end-stage OA group had higher age (p < 0.0001), body mass index (p = 0.0061), Charlson comorbidity index (<0.0001), and OA classification (p < 0.0001). Preoperative KOOS were similar between the groups. Interleukin-6 (IL-6) and IL-8 were elevated in the end-stage OA group compared with the knee injury group (p = 0.04 and 0.006, respectively). Granulocyte-macrophage colony-stimulating factor, interferon gamma, IL-1ß, IL-12p70, IL-2, IL-10, and tumor necrosis factor alpha were not statistically different between the groups. A similar synovial fluid cytokine profile was found between the two groups. The elevation of IL-6 and IL-8 in the end-stage OA group indicates the potential role that these proinflammatory cytokines may have in long-term cartilage damage.

The complement system is activated in synovial fluid from subjects with knee injury and from patients with osteoarthritis.

BACKGROUND: The complement system is suggested to be involved in the pathogenesis of osteoarthritis (OA), and proinflammatory cytokines may play a role in OA development by inducing proteases. The association between complement factors, cytokines and OA has not been investigated. The aim of the present study was to explore the involvement of the complement system after knee trauma and in OA. METHODS: C4d, C3bBbP and soluble terminal complement complex (sTCC) resulting from complement activation were immunoassayed in synovial fluid from subjects with healthy knees (reference), OA, rheumatoid arthritis (RA; positive control), pyrophosphate arthritis (PPA; positive control) and knee injury; other biomarkers were previously assessed. Magnetic resonance imaging was used to assess joint injuries. RESULTS: Compared with levels in the reference group, the median concentrations of C4d, C3bBbP and sTCC in the OA, RA, PPA and knee injury groups were 2- to 34-fold increased (p < 0.001 to p = 0.044). For the knee injury group, the median concentrations of C4d, C3bBbP and sTCC were 5- to 12-fold increased (p < 0.001) at the day of injury; after 3-12 weeks, C3bBbP and sTCC concentrations were similar to reference levels; and C4d was still increased several years after injury. In the 0-12 weeks period after injury, the concentrations of C4d, C3bBbP and sTCC correlated positively with levels of interleukin (IL)-1ß, IL-6 and tumour necrosis factor α (r s range 0.232-0.547); none of the measured complement factors correlated with proteolytic fragments of aggrecan or cartilage oligomeric matrix protein. Knees with osteochondral fracture, with or without disrupted cortical bone, had higher concentrations of C4d (p = 0.014, p = 0.004) and sTCC (p = 0.004, p < 0.001) compared with knees without fractures. CONCLUSIONS: The complement system is activated in OA and after knee injury. Following knee injury, this activation is instant and associated with inflammation as well as with the presence of osteochondral fractures.

Synovial chemokine expression and relationship with knee symptoms in patients with meniscal tears.

OBJECTIVE: In patients with knee OA, synovitis is associated with knee pain and symptoms. We previously identified synovial mRNA expression of a set of chemokines (CCL19, IL-8, CCL5, XCL-1, CCR7) associated with synovitis in patients with meniscal tears but without radiographic OA. CCL19 and CCR7 were also associated with knee symptoms. This study sought to validate expression of these chemokines and association with knee symptoms in more typical patients presenting for meniscal arthroscopy, many who have pre-existing OA. DESIGN: Synovial fluid (SF) and biopsies were collected from patients undergoing meniscal arthroscopy. Synovial mRNA expression was measured using quantitative RT-PCR. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was administered preoperatively. Regression analyses determined if associations between chemokine mRNA levels and KOOS scores were independent of other factors including radiographic OA. CCL19 in SF was measured by ELISA, and compared to patients with advanced knee OA and asymptomatic organ donors. RESULTS: 90% of patients had intra-operative evidence of early cartilage degeneration. CCL19, IL-8, CCL5, XCL1, CCR7 transcripts were detected in all patients. Synovial CCL19 mRNA levels independently correlated with KOOS Activities of Daily Living (ADL) scores (95% CI [-8.071, -0.331], P = 0.036), indicating higher expression was associated with more knee-related dysfunction. SF CCL19 was detected in 7 of 10 patients, compared to 4 of 10 asymptomatic donors. CONCLUSION: In typical patients presenting for meniscal arthroscopy, synovial CCL19 mRNA expression was associated with knee-related difficulty with ADL, independent of other factors including presence of radiographic knee OA.

Meniscal tear as potential steering factor for inflammation may aggravate arthritis: two case reports.

INTRODUCTION: Meniscal tear is thought to play a crucial role in onset as well as progression of arthritis. However, role of cytokine response to meniscal injury and resulting inflammation is not clearly understood. Because synovial fluid is juxtaposed to cartilage and serves as a biological connection between chondrocytes and synoviocytes, we chose synovial fluid analysis to ascertain biochemical response associated with a meniscal tear. CASE PRESENTATION: We report the cases of two patients with clinically different inflammatory arthritis, both of whom are Indian men. Patient 1 was 30 years of age, and patient 2 was 50 years of age. They both had a history of meniscal tear, which we confirmed by magnetic resonance imaging scans. Synovial fluid samples obtained from these two patients were analyzed for proinflammatory markers, such as interleukin 1ß (IL-1ß) and nitric oxide, and also for glycosaminoglycan as a cartilage degradation indicator. Relatively high levels of IL-1ß (2000.0 ± 15.7 pg/ml) and nitric oxide (4.73 ± 0.05 µM/ml) and relatively low glycosaminoglycan (93.75 ± 6.3 µg/ml) were observed in patient 1, corroborating the diagnosis of traumatic meniscal tear. Compared to patient 1, Patient 2 had relatively low levels of IL-1ß (54.55 ± 14.5 pg/ml) and nitric oxide (20.00 ± 0.6 µM/ml) and remarkably high glycosaminoglycan levels (553.33 ± 1.7 µg/ml), coupled with significant osteophytes and profound cartilage loss, which indicated severe arthritis and a diagnosis of degenerative meniscal tear. CONCLUSION: The elevated levels of inflammatory IL-1ß aggravated the severity of arthritis attributable to meniscal tear in both patients, as found in follow-up visits. This was quite evident in patient 2, whereas patient 1, being younger, had less serious symptoms. Meniscal tear has emerged as a potential confounding factor in arthritis with different clinical backgrounds, which leads to increased levels of inflammation and results in accelerated disease progression.

Mesenchymal stem cells in synovial fluid increase after meniscus injury.

BACKGROUND: Although relatively uncommon, spontaneous healing from a meniscus injury has been observed even within the avascular area. This may be the result of the existence of mesenchymal stem cells in synovial fluid. QUESTIONS/PURPOSES: The purpose of this study was to investigate whether mesenchymal stem cells existed in the synovial fluid of the knee after meniscus injury. METHODS: Synovial fluid was obtained from the knees of 22 patients with meniscus injury just before meniscus surgery and from 8 volunteers who had no history of knee injury. The cellular fraction of the synovial fluid was cultured for 14 days followed by analysis for multilineage potential and presentation of surface antigens characteristic of mesenchymal stem cells. Colony-forming efficiency and proliferation potential were also compared between the two groups. RESULTS: Cells with characteristics of mesenchymal stem cells were observed in the synovial fluid of injured knees to a much greater degree than in uninjured knees. The colony-forming cells derived from the synovial fluid of the knee with meniscus injury had multipotentiality and surface epitopes identical to mesenchymal stem cells. The average number of colony formation, obtained from 1 mL of synovial fluid, in meniscus-injured knees was 250, higher than that from healthy volunteers, which was 0.5 (p < 0.001). Total colony number per synovial fluid volume was positively correlated with the postinjury period (r = 0.77, p < 0.001). CONCLUSIONS: Mesenchymal stem cells were found to exist in synovial fluid from knees after meniscus injury. Mesenchymal stem cells were present in higher numbers in synovial fluid with meniscus injury than in normal knees. Total colony number per synovial fluid volume was positively correlated with the postinjury period. CLINICAL RELEVANCE: Our current human study and previous animal studies suggest the possibility that mesenchymal stem cells in synovial fluid increase after meniscus injury contributing to spontaneous meniscus healing.

[Lateral superior genicular flap combined with Tuihuang xiaozhong decoction for the treatment of soft tissue defects around the knee joint].

OBJECTIVE: To evaluate the early combination of Chinese and Western medicine for anti-inflammation and lateral superior genicular flap for the treatment of soft tissue defects around the knee joint. METHODS: From June 2004 to September 2008, 8 patients with soft tissue defects around the knee joint were treated with lateral superior genicular flap. Among the patients, 5 patients were male and 3 patients were female, ranging in age from 32 to 56 years, with an average of 35.2 years. The defected area ranged from 7.6 cm x 4.5 cm to 15.2 cm x 7.5 cm. The disease course ranged from 3 months to 3 years. Three patients had the defects at the posterior of the knee, 2 patients had the defects at the popliteal fossa, and 3 patients had the defects at the lateral side of the knee. At the early stage, all the patients were treated with Tuihuang Xiaozhong decoction and antibiotics for 3 to 5 days. RESULTS: All the flaps survived, and the knee function recovered. One patient had epidermis necrosis at the distal end of the flap of lateral side of the knee. CONCLUSION: The early combination of Chinese and Western medicine for anti-inflammation is a simple, easy to promote, and no special microsurgical instruments are needed.

Joint injury and osteoarthritis: soluble mediators in the course and treatment of cartilage pathology.

Osteoarthritis is a disabling disease of the aging generation, which results in loss of quality of life and increased healthcare costs. Cytokines appear to play an important role in the cartilaginous degeneration characterizing the pathological process. Increasing experience is being gained with cytokine-modulating therapies aimed at interfering with effects of chondrodegradative cytokines in the synovial fluid. Although in vitro and in vivo effectiveness of several of these therapies has been demonstrated, clinical effectiveness remains disputable, which may be related to the low levels of inflammatory cytokines found in osteoarthritic joints. By contrast, directly after joint trauma, which has been shown to predispose to early osteoarthritis, synovial fluid cytokine levels are strongly increased. Cytokine-modulating therapies, however, have hardly been considered for this indication. Increased knowledge of intra-articular soluble mediators correlating with cartilage pathology will lead to further development of cytokine-modulating products and, eventually, to effective inhibition of cartilage degeneration, in both the osteoarthritic as well as injured joints.

Activating and inhibitory receptors on synovial fluid natural killer cells of arthritis patients: role of CD94/NKG2A in control of cytokine secretion.

Natural killer (NK) cells are activated early during inflammatory events and contribute to the shaping of the ensuing adaptive immune response. To further understand the role for NK cells in inflammation, we investigated the phenotype and function of synovial fluid (SF) NK cells from patients with chronic joint inflammation, as well as from patients with transient inflammation of the knee following trauma. We confirm that synovial NK cells are similar to the well-characterized CD56(bright) peripheral blood (PB) NK-cell subset present in healthy individuals. However, compared to this PB subset the synovial NK cells express a higher degree of activation markers including CD69 and NKp44, the latter being up-regulated also on CD56(bright) NK cells in the PB of patients. Activated synovial NK cells produced interferon-gamma and tumour necrosis factor, and the production was further up-regulated by antibody masking of CD94/NKG2A, and down-regulated by target cells expressing human leucocyte antigen-E in complex with peptides known to engage CD94/NKG2A. We conclude that synovial NK cells have an activated phenotype and that CD94/NKG2A is a key regulator of synovial NK-cell cytokine synthesis.

Therapeutic ultrasound enhances medial collateral ligament repair in rats.

The purpose of this study was to evaluate the effects of therapeutic ultrasound (US) on medial collateral ligament healing. A total of 36 3-month-old male Sprague-Dawley rats with transected medial collateral ligaments were studied. Subjects were given 5-min pulsed US therapy (duty cycle; one application in 4 ms; 1:4) daily with different durations (1 day, 5 days and 10 days) and intensities (0, 0.5 and 2.3 W/cm2). After each treatment, the level of transforming growth factor beta-1 (TGF-beta1) of the ligament was measured. TGF-beta1 was not detected in the 1-day group. In the 5-day and 10-day groups, the levels of TGF-beta1 were significantly up-regulated in the high-dose subgroup (p < 0.05). The 10-day group also registered a significantly higher expression of TGF-beta1 than did the 5-day group (p < 0.05). The present findings suggest that pulsed US therapy may enhance ligament repair by up-regulating the extent of TGF-beta1 in a high-dose application. Long-term treatment with this therapy could obtain further improvement.

Substance P immunoreactive fibers of synovial tissue in patients with anterior cruciate ligament injury.

Substance P, a neuropeptide, exerts proinflammatory effects and transmits the sensation of pain. Substance P immunoreactive fibers of the synovial tissue were examined to investigate the significance of Substance P in the traumatic joint. Biopsy specimens from 15 patients (eight female and seven male) with anterior cruciate ligament (ACL) injury were examined immunohistochemically with semi-quantitative counting to correlate Substance P positive fibers of the synovial tissue with clinical data, pain intensity on a visual analog scale, and serous inflammatory indicators. The total (sum of the three compartments) expression of Substance P in females of 571.9+/-255.1 cm(-2) was significantly greater than that of males of 241.2+/-126.6 cm(-2). In the female group, the total number of Substance P immunoreactive fibers was significantly correlated with pain intensity (r=0.804); in the male group, there was no significant correlation with pain intensity. The expression of Substance P in the female infrapatellar fat pad was statistically significantly correlated with pre- and postoperative erythrocyte sedimentation rate as inflammation indicators. In the male group, there was no such correlation. Substance P was well- correlated with pain and inflammatory reaction in the female joint. Neural inflammation and neural pain occur more strongly in female joints.

Enhancement of the repair of meniscal wounds in the red-white zone (middle third) by the injection of bone marrow cells in canine animal model.

Bone marrow stem cells (BMSCs) can differentiate into several cells that participate in the healing of meniscal wounds. To test this hypothesis, we examined the effects of injected BMSCs on the healing of meniscal wounds. Autologous BMSCs from eight adult dogs were injected into meniscal wounds (knee joints). After 12 weeks, the healing process was clinically and immunomorphologically evaluated using: (i) histochemical stains (haematoxylin and eosin, Masson trichrome and periodic acid-Schiff) and (ii) immunoperoxidase staining methods (CD3, CD79a, CD68, CD31 and alpha smooth-muscle actin for T, B lymphocytes, macrophages, endothelial cells and smooth-muscle lineage). Complete (six vs. three), partial (one vs. one) and no healing (one vs. four animals) of the meniscal wounds were observed in the injected and noninjected menisci. As compared with the noninjected menisci, examination of the tissues from the injected ones revealed: (i) marked angiogenesis (microvessel density: 3.22 +/- 0.66 vs. 6.50 +/- 2.10); (ii) chondrogenesis; (iii) prominent immune cell infiltrate (4.07 +/- 0.78 vs. 9.56 +/- 1.69, 8.33 +/- 0.77 vs. 3.67 +/- 1.00 and 4.38 +/- 0.62 vs. 11.1 +/- 1.43 for the total numbers of immune cells, lymphocytes and macrophages, respectively); and (iv) proliferation of the fibroblasts with marked deposition of collagen fibres (2.0 +/- 0.84 vs. 2.66 +/- 0.48). These values were statistically significantly higher for the injected menisci as compared with the noninjected ones (P >/= 0.05). Autologous BMSCs can improve meniscal wound healing. Whether this improvement occurs through BMSC differentiation into cells operational in the repair process, the release of certain mediator or other unknown mechanisms mandates further investigations.

Immune response in patients receiving fresh osteochondral allografts.

Immunologic response to cartilage-specific protein (CSP) antigens was tested in patients treated with fresh osteochondral allografts. Eight of 14 allograft recipients showed immune reactivity against CSP, whereas only 2 of 14 controls were reactive (P<.05). The molecular weights of the most common immunoreactive proteins were 220 kd and 95 kd. The precise identity of these proteins could not be determined using standard anticollagen antibodies. These data indicate the presence of antibodies to CSP--which supports the concept of immunologic response to the cartilage component of osteochondral allografts.

Arthrofibrosis is the result of a T cell mediated immune response.

It is thought that an excessive fibrotic healing response with diffuse intra-articular scarring leads to arthrofibrosis after trauma and surgery around joints. To clarify the specific cellular mechanism of arthrofibrosis during arthrolysis we took fibrotic tissue samples from 18 patients at varying periods after knee trauma or surgery. Sections were stained with hematoxylin and eosin to study the overall histopathological changes. Major histocompatibility complex (MHC) class II expressing cells as well as CD3, CD4, CD25, CD28, CD68, CD80, and CD83 positive cells were localized immunohistologically. The results demonstrated synovial hyperplasia with fibrotic enlargement of the subintima and infiltration of inflammatory cells. The number of MHC class II expressing cells was increased. Mainly, intimal macrophages and dendritic cells showed positive immunostaining for MHC class II antigens. In the subintima moderate infiltration of T cells including activated T cells (CD25), CD4+ T helper (Th) cells and Th1 and Th2 subsets was detected. There was a slight polarization of the Th1/Th2 balance towards Th1 differentiation. Positive immunostaining for CD80/CD28 indicated the costimulatory signal for T cell activation and clonal expansion. These findings strongly support an immune response as the cause of capsulitis leading to formation of diffuse scar tissue within the knee joint. Based on our immunohistological study we conclude that a T cell mediated immune response plays a crucial role in the mechanism of arthrofibrosis.

In vivo microdialysis and immunohistochemical analyses of tendon tissue demonstrated high amounts of free glutamate and glutamate NMDAR1 receptors, but no signs of inflammation, in Jumper's knee.

This investigation describes, to our knowledge, the first experiment where the microdialysis technique was used to study certain metabolic events in human patellar tendons in combination with immunohistochemical analyses of tendon biopsies. In five patients (four men and one woman) with a long duration (range 12-36 months) of pain symptoms from Jumper's knee (localized tenderness in the patellar tendon verified as tendon changes with ultrasonography or MRI), and in five controls (four men and one woman) with normal patellar tendons, a standard microdialysis catheter was inserted into the patellar tendon under local anestesia. The local concentrations of glutamate (excitatory neurotransmitter) and prostaglandin E2 (PGE2) were registered under resting conditions. Samplings were done every 15 min during a 2 h period. In all individuals (patients and controls) biopsies were taken for immunohistochemical analyses. The results showed that it was possible to detect and measure the concentrations of glutamate and PGE2 in the patellar tendon with the use of microdialysis technique. There were significantly higher concentrations of free glutamate, but not PGE2, in tendons with tendinosis compared to normal tendons. In the biopsies, there were no inflammatory cell infiltrates, but, for the first time, it was shown that there was immunoreaction for the glutamate receptor NMDAR1 in association with nerve structures in human patellar tendons. These findings altogether indicate that glutamate might be involved in painful Jumper's knee, and further emphasizes that there is no chemical inflammation (normal PGE2 levels) in this chronic condition.

Shell osteochondral allografts of the knee: comparison of mr imaging findings and immunologic responses.

PURPOSE: To define the magnetic resonance (MR) imaging appearance of shell osteochondral allografts of the knee and compare the MR findings with antibody responses. MATERIALS AND METHODS: Thirty-six grafts were evaluated with a 1.5-T unit with T1-, intermediate-, and T2-weighted, and three-dimensional spoiled gradient-recalled MR imaging at 3, 6, 12, 24, and/or 36 months after surgery. Nineteen patients underwent imaging serially. Two osteoradiologists scored by consensus host marrow edema, thickness of graft-host interface, signal intensity of graft marrow, cyst formation, joint effusion, articular cartilage defects, and surface collapse. Patients were divided into antibody-positive (AP) (n = 11) and antibody-negative (AN) (n = 25) groups evenly distributed across the different time points on the basis of results of anti-human leukocyte antigen antibody screening. MR findings for the two groups were compared. RESULTS: AP patients demonstrated greater mean edema (P<.002), thicker interface (P<.03), and more abnormal graft marrow (P<.04) than AN patients, and they had a higher proportion of surface collapse (P<.03). CONCLUSION: Humoral immune responses were associated with more inflammation and less complete incorporation after allograft placement. MR imaging shows promise as a surrogate biomarker for success of shell osteochondral allograft implantation.

Matrix metalloproteinase-19 in capillary endothelial cells: expression in acutely, but not in chronically, inflamed synovium.

Matrix metalloproteinase-19 (MMP-19), originally isolated as an autoantigen from the synovium of a patient suffering from rheumatoid arthritis (RA), is expressed in smooth muscle cells of the tunica media of large blood vessels of an RA patient, but not in the endothelial cell layer. By contrast, in acutely inflamed tissue, synovial capillaries strongly express MMP-19 in the cytoplasm, as shown by immunofluorescence of cryostat sections. In MMP-19-producing capillaries the beta3 integrin chain was found at the endothelial cell surface, as was the vascular endothelial cell growth factor receptor-2 (KDR). The specific tissue inhibitor of metalloproteinases TIMP-1 was absent or faintly stained in MMP-19-expressing capillaries, whereas TIMP-1, but not TIMP-2, was strongly expressed in large vessels and in MMP-19-negative capillaries of RA synovia. In the spontaneously transformed human umbilical vein endothelial cell line ECV304 neither MMP-19 transcripts nor protein could be detected. By contrast, primary cultures of human endothelial cells of either dermal or adipose tissue origin produced MMP-19 mRNA and protein. The results strongly suggest the regulated induction of matrix metalloproteinase-19 in capillary endothelial cells during acute inflammation and hint at a role of MMP-19 in angiogenesis.