On the edge of decision-making in trauma care: A focus group study on radiographers' experiences of interprofessional collaboration.

INTRODUCTION: The temporary trauma teams in trauma alerts consist of a diverse group of unique professionals requiring interprofessional collaboration and coordination to achieve efficient, high-quality care. The uncertain situation and complex care environment impose high demands on team dynamics such as individual attitudes and team behaviours. Within interprofessional teams, interaction and coordination reflect the collective success of collaboration and the achievement of goals. Interactions with radiographers have increased in trauma teams given computed tomography's prominent role in providing crucial knowledge for decision-making in trauma care. This study aimed to explore radiographers' experiences of interprofessional collaboration during trauma alerts. METHOD: The study was designed with focus group methodology, including 17 radiographers participating in five focus groups, analysed with an inductive focus group analysis. RESULTS: An overarching theme, "On the edge of decision-making", emerged along with three sub-themes: "Feeling included requires acknowledgement", "Exclusion precludes shared knowledge", and "Experience and mutual awareness facilitate team interaction". CONCLUSIONS: Interprofessional collaboration from the radiographer's perspective within trauma teams requires a sense of inclusion and the ability to interact with the team. Exclusion from vital decision-making obstructs radiographers' comprehension of situations and thereby the interdependence in interprofessional collaboration. IMPLICATIONS FOR PRACTICE: Common platforms are needed for knowledge sharing and team practices, including radiographers' areas of responsibility and relational coordination to foster interprofessional relationships. Through these means interdependence through awareness and shared knowledge can be facilitated on trauma teams.

Relation between dorsal and palmar hand skin temperatures during a cold stress test.

Hand skin temperature measurements have previously been performed on either dorsal or palmar sides and it is possible to find arguments for the advantage of both locations. Therefore, the aim of this study was to use dynamic infrared (IR) imaging to examine the relationship between dorsal and palmar hand skin temperature. The palmar and dorsal hand skin temperature before and after a cold stress test was measured with IR thermography in 112 healthy participants. Calculation of surface average temperature was made from nine regions of interest on each hand's dorsal and palmar side. Temperature values were recorded at baseline, directly after immersion of hands in vinyl gloves for one minute in water at 20 ±0.5 °C (gloves removed), and after eight minutes rewarming. Results showed that: a) the skin temperatures on the dorsal and palmar sides of the hand are strongly correlated; b) the correlation is stronger on the fingers than on the carpometacarpal (CMC) area; c) the palmar side of the CMC area is warmer than the dorsal side, but this is reversed in the fingers so that the nail bed is warmer than the finger pad; and d) the temperature difference ∆T between the dorsal and palmar sides of the fingers is independent of the skin temperature, though ∆T on the CMC area of the hand is temperature dependent. Such differences can be important in detailed investigations of thermal phenomena in the hand. In conclusion, results showed a strong correlation between the dorsal and palmar temperatures. If both sides cannot be measured, the purpose of the investigation should determine which side of the hand should be measured.

Coastal sediments in the Gulf of Bothnia as a source of dissolved PCDD/Fs and PCBs to water and fish.

High levels of PCDD/Fs and PCBs in Baltic Sea biota have been a matter of great concern during the last decades. We measured the freely dissolved concentrations of PCDD/Fs and PCBs in sediment pore water and bottom water in eight areas along the Swedish coast of the Gulf of Bothnia, by using state-of-the-art passive samplers. Chemical activity ratios (calculated from freely dissolved concentrations in pore water and bottom water based on chemical activity ratios) for PCDD/Fs were higher than 1 at all stations (PCDD/Fs average 27; stdev 22). High activity ratios suggest that the sediments have a potential to act as a source of dissolved PCDD/Fs to the water column. Activity ratios for PCBs varied between 0.3 and 17 (average 2; stdev 4). The concentrations of PCDD/Fs and PCBs in bottom water were significantly correlated with concentrations in sediment pore water (p<0.00001 to p=0.03) as well as with concentrations in juvenile perch caught in the same areas (p<0.00001 to p=0.02). To our knowledge, this is the first study demonstrating a correlation between in-situ measured freely dissolved PCDD/F concentrations and lipid-normalized contents in stationary fish. Our results confirm that freely dissolved concentrations should be used as chemical predictors of bioaccumulation. The results from this study imply that continued efforts to reduce levels of PCDD/Fs and PCBs in coastal sediments will have positive effects on concentrations of these contaminants in lower trophic levels of Baltic Sea ecosystems.

Changes in chemokines and their receptors in blood during treatment with the TNF inhibitor infliximab in patients with rheumatoid arthritis.

OBJECTIVES: Chemokines are involved in leucocyte recruitment into inflammatory sites. The release of certain chemokines is augmented by tumour necrosis factor (TNF). Infliximab, a monoclonal antibody that blocks the effects of TNF, is used for treatment of rheumatoid arthritis (RA). The effect of TNF blockage on chemokines is not fully understood. The aim of this study was to analyse the effects on chemokines and their receptors on peripheral mononuclear cells of anti-TNF treatment in RA patients. METHOD: Twelve patients with established RA who started treatment with infliximab and nine patients with early RA treated with other anti-rheumatic drugs were followed clinically for 30 weeks and chemokine levels in blood samples were analysed along with chemokine receptor expression on the surface of T cells and monocytes. Nine healthy subjects were included as a control group. RESULTS: The chemokine CXCL10/IP-10 was significantly higher in RA patients than in healthy controls (p = 0.012). Two weeks after infliximab infusion, CXCL10/IP-10, CCL2/MCP-1, and CCL4/MIP-1ß had decreased significantly (p = 0.005, 0.037, and 0.028, respectively), and after 30 weeks of treatment, soluble CD26 was significantly increased (p = 0.050). Several chemokine receptors on T cells were elevated in RA patients at inclusion. The expression of CCR2 and CXCR1 on T cells decreased significantly after infliximab treatment. CONCLUSIONS: The chemokines CXCL10/IP-10, CCL2/MCP-1, and CCL4/MIP-1ß, mainly targeting the T-helper (Th)1 immune response, decreased after treatment with anti-TNF, suggesting a more pronounced effect on Th1 activity than on Th2-mediated response. Several chemokine receptors on blood T cells were elevated in RA patients, suggesting that they may be involved in the recruitment of T lymphocytes from the blood to affected tissues.

PCDD/F source apportionment in the Baltic Sea using positive matrix factorization.

Positive Matrix Factorization (PMF) was used to identify and apportion candidate sources of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) in samples of offshore and coastal surface sediments from the Baltic Sea. Atmospheric deposition was the dominant source in offshore and pristine areas, in agreement with previous studies. Earlier chlorophenol use and a source suggested origins from pulp and paper production and related industries were identified as important coastal sources. A previously presumed major source, chlorine bleaching of pulp, was of only minor importance for modern Baltic surface sediments. The coastal source impacts were mostly local or regional, but pattern variations in offshore samples indicate that coastal sources may have some importance for offshore areas. Differences between sub-basins also indicated that local and regional air emissions from incineration or other high-temperature processes are more important in the southern Baltic Sea compared to those in northerly areas. These regional differences demonstrated the importance of including offshore sediments from the Bothnian Bay, Gulf of Finland, and other areas of the Baltic Sea in future studies to better identify the major PCDD/F sources to the Baltic Sea.

Receptor communication within the lymphocyte plasma membrane: a role for the thrombospondin family of matricellular proteins.

Lymphocytes, the principal cells of the immune system, carry out immune surveillance throughout the body by their unique capacity to constantly reposition themselves between a free-floating vascular state and a tissue state characterized by migration and frequent adhesive interactions with endothelial cells and components of the extracellular matrix. Therefore, mechanisms co-ordinating adhesion and migration with signals delivered through antigen recognition probably play a pivotal role for the regulation of lymphocyte behaviour and function. Endogenous thrombospondin-1 (TSP-1) seems to be the hub in such a mechanism for autocrine regulation of T cell adhesion and migration. TSP-1 functions as a mediator of cis interaction of vital receptors within the T lymphocyte plasma membrane, including integrins, low density lipoprotein receptor-related protein, calreticulin and integrin-associated protein.

Limits on spin-independent interactions of weakly interacting massive particles with nucleons from the two-tower run of the cryogenic dark matter search.

We report new results from the Cryogenic Dark Matter Search (CDMS II) at the Soudan Underground Laboratory. Two towers, each consisting of six detectors, were operated for 74.5 live days, giving spectrum-weighted exposures of 34 (12) kg d for the Ge (Si) targets after cuts, averaged over recoil energies 10-100 keV for a weakly interacting massive particle (WIMP) mass of 60 GeV/c2. A blind analysis was conducted, incorporating improved techniques for rejecting surface events. No WIMP signal exceeding expected backgrounds was observed. When combined with our previous results from Soudan, the 90% C.L. upper limit on the spin-independent WIMP-nucleon cross section is 1.6 x 10(-43) cm2 from Ge and 3 x 10(-42) cm2 from Si, for a WIMP mass of 60 GeV/c2. The combined limit from Ge (Si) is a factor of 2.5 (10) lower than our previous results and constrains predictions of supersymmetric models.

Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNF alpha.

BACKGROUND: Research on autoantibody formation in patients treated with TNF alpha inhibitors has produced contradictory results. OBJECTIVE: To study the prevalence of autoantibodies in patients with rheumatoid arthritis treated with the TNF alpha inhibitor infliximab. METHODS: 53 patients (48 female, 11 male) treated with infliximab for rheumatoid arthritis were followed for autoantibody production before treatment and after 14, 30, and 54 weeks. Six patients treated with etanercept were studied for comparison. The analyses included antibodies against nuclear antigens (ANA), extractable nuclear antigens, double stranded (ds)DNA (by ELISA, IIF on Crithidia luciliae for IgM and IgG, and Farr assay), nucleosomes, cardiolipin, smooth muscle, mitochondria, proteinase 3, and myeloperoxidase antigens. RESULTS: The number of patients treated with infliximab who developed antibodies against dsDNA of both IgG and IgM class (tested by IIF) increased significantly. The prevalence of patients positive for IgG class increased to 66% at 30 weeks and 45% at 54 weeks, and of IgM class to 85% and 70%, respectively. The titre and number of patients expressing antibodies against nucleosomes and ANA also increased significantly. The number of rheumatoid factor or anticardiolipin positive patients was stable and there was no increase in antibodies against the other antigens. A lupus-like syndrome was seen in one patient. No patient treated with etanercept developed any of these autoantibodies. CONCLUSIONS: Patients treated with infliximab may develop anti-dsDNA antibodies of both IgM and IgG class, anti-nucleosome antibodies, and ANA, with a gradual increase until 30 weeks.

Somatostatin is a specific inhibitor of SDF-1alpha-induced T cell infiltration.

The chemokine stromal cell-derived factor 1alpha (SDF-1alpha) is a potent stimulator of T cell infiltration into three-dimensional type I collagen matrices as demonstrated using T cells freshly isolated from blood and an activated T cell clone. The neuropeptide somatostatin selectively inhibits SDF-1alpha induced T cell infiltration by the same T cells including CD4 as well as CD8 positive cells, while somatostatin does not inhibit 'spontaneous' T cell infiltration. A number of other neuropeptides and opioids do not inhibit SDF-1alpha-induced T cell infiltration, indicating that the inhibitory effect is somatostatin-specific. The neuropeptide antagonist cyclosomatostatin abrogated the inhibitory effect of somatostatin on T cell infiltration, indicating that the effect of somatostatin is mediated via specific somatostatin receptors. Somatostatin does not inhibit SDF-1alpha-induced T cell attachment to the collagen substrate, which indicates that this neuropeptide specifically inhibits the process of chemokine-induced T cell penetration and migration through the collagen.

Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus.

The expression of chemokine receptors on T-cells and chemokine levels in the blood was studied in 23 patients with SLE (ACR criteria), seven patients with rheumatoid arthritis (RA) and in 15 healthy controls using flow cytometry, RT-PCR and ELISA. The cell surface expression of the chemokine receptors CXCR5 and CCR6 was decreased in SLE patients compared with controls (P = 0.051 and P = 0.002, respectively). The decrease of CXCR5 was confined to SLE patients with inactive disease (SLEDAI < 6) compared with active disease (SLEDAI > 6) and controls. CXCR2 and CCR1 were increased in patients with active SLE compared with patients with inactive disease (P = 0.001 and P = 0.01, respectively) and with controls (P = 0.02 and P = 0.053, respectively). The levels of the chemokines MIP-1alpha MCP-1, SDF-1alpha, IP-10 and RANTES were significantly elevated in SLE patients compared with controls. Patients with renal involvement had increased surface expression of CXCR3 and CCR3 (P = 0.04 in both) and a lower level of soluble IP-10 compared with patients without renal disease (P = 0.025) and compared with controls (P = 0.001). The ratio between CCR5 and CCR3 was significantly increased in RA patients compared with SLE patients and controls supporting a Th1 overweight in RA. In conclusion, patients with SLE showed abnormal T-cell expression of several chemokine receptors and levels of soluble chemokines in their plasma/serum.

Somatostatin receptor (SSTR) expression and function in normal and leukaemic T-cells. Evidence for selective effects on adhesion to extracellular matrix components via SSTR2 and/or 3.

We have examined normal T-cells and T-cell lines with respect to expression of various somatostatin receptor subtypes (SSTR1--5) using RT-PCR and PCR. To evaluate the function of these receptors we have further studied the effects of subtype specific signalling on T-cell adhesion using somatostatin analogs specific for various receptors as probes. Human T-lymphocytes showed SSTR expression related to activation and stage of differentiation. Normal T-cells (peripheral blood, T-cell clone) and T-leukaemia cell lines expressed SSTR2, SSTR3 and SSTR4. Normal T-cells expressed SSTR1 and SSTR5 while T-leukaemia lines did not. SSTR5 was selectively expressed in activated normal T-cells. T-lymphocytes produced no somatostatin themselves. Somatostatin and somatostatin analogs specific for SSTR2 and/or SSTR3 enhanced adhesion of T-cells to fibronectin (FN), and to a certain extent, also to collagen type IV (CIV) and laminin (LAM). T-lymphocytes express multiple SSTR and somatostatin may therefore regulate lymphocyte functions via distinct receptor subtypes as shown here for adhesion to extracellular matrix components (ECM) via SSTR2 and SSTR3. SSTR expression also distinguishes normal and leukaemic T-cells. Our findings suggest that SSTR subtypes may be useful targets for therapy during inflammatory diseases and malignancies affecting lymphocytes.

Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women.

OBJECTIVE: To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink. DESIGN: Open, randomised controlled 12 month follow up trial. SETTING: Health centres for university students and staff of university hospital. PARTICIPANTS: 150 women with urinary tract infection caused by Escherichia coli randomly allocated into three groups. INTERVENTIONS: 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention. MAIN OUTCOME MEASURE: First recurrence of symptomatic urinary tract infection, defined as bacterial growth >/=10(5 )colony forming units/ml in a clean voided midstream urine specimen. RESULTS: The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34). CONCLUSION: Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection.

The regulation of FasL expression--a distinquishing feature between monocytes and T lymphocytes/NK cells with possible implications for SLE.

Monocytes and lymphocytes from patients with systemic lupus erythematosus (SLE) had a higher cell surface expression of FasL than the corresponding cells from healthy individuals. Inhibitors of metalloproteases upregulated the surface expression of FasL in peripheral blood lymphocytes (PBL), indicating that a metalloprotease is responsible for the cleavage of FasL. The level of sFasL in serum was slightly increased in the patient group compared to the controls. Therefore, the possible contribution of various mononuclear cell types to the release of FasL was analyzed. Isolated NK cells and T lymphocytes released FasL into the medium and the release was prevented by inhibitors of metalloproteases. In contrast, isolated monocytes did not release FasL. FasR expression was elevated in patients with inverted CD4/CD8 ratio, while FasL expression showed no relationship to CD4/CD8 ratio. The absence of FasL release by isolated cells and a high level of surface expression of FasL distinguish monocytes and T lymphocytes/NK cells.

Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis.

OBJECTIVE: To measure the extent of atherosclerosis in patients with rheumatoid arthritis (RA) with a disease duration of considerable length, and in age and sex matched individuals. METHODS: Thirty-nine patients with RA (30 women, 9 men) with disease onset occurring between 1974 and 1978, and less than 65 years of age at the time of investigation, were enrolled together with 39 sex and age matched controls. Quantitative measurement of intima-media thickness (IMT) and semiquantitative assessment of the presence of plaque were undertaken by B-mode ultrasound of the common carotid artery (CCA-IMT) and the common femoral artery on the right-hand side. Echo Doppler cardiography was performed with an Accuson Aspen. The results were related to disease activity variables and accumulated disease activity, to lipid levels [i.e., cholesterol, high density lipoproteins, low density lipoproteins, triglycerides (TG)], to hemostatic factors [tissue plasminogen activator antigen (tPAag), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF)], and to soluble adhesion molecules (sICAM-1 and sE-selectin). RESULTS: Patients with RA had higher maximal and mean IMT values compared with controls. The difference concerning mean CCA-IMT reached statistical significance in patients with RA and correlated significantly with lipids (cholesterol, LDL, LDL/HDL ratio, TG) and tPAag. The prevalence of plaques, as well as of aortic cusp sclerosis, was higher in RA but only the difference in aortic cusp sclerosis was statistically significant. Patients with plaques had significantly higher levels of lipids (cholesterol, LDL, LDL/HDL ratio) than patients without plaques, while patients with cusp sclerosis had significantly higher cholesterol and TG levels. sICAM-1 was significantly higher both in patients with plaques and in those with aortic cusp sclerosis compared to patients without. CONCLUSION: Our results suggest an accelerated atherosclerosis in patients with RA that is related mainly to lipid levels.

Defective chemokine production in T-leukemia cell lines and its possible functional role.

Peripheral blood lymphocytes and T-cell clones produced nanogram quantities of the chemokines RANTES, MIP-1alpha, MIP-1beta, MCP-1, IL-8 and GRO-alpha as well as the motogenic cytokine HGF. In contrast, various T-leukemia cell lines at different stages of differentiation did not produce the same chemokines/cytokines. In order to study the possible functional importance of the poor chemokine production different T-cell lines were compared with respect to development of motile forms and migration on extracellular matrix components in the absence and presence of various chemokines. RANTES, MIP-1alpha, MIP-1beta, IL-8, GRO-alpha and lymphotactin did not augment the development of motile forms including the size and appearance of the pseudopodia activity of the T-leukemia cell lines. The T-cell lines migrated spontaneously on/to fibronectin in a Boyden chamber assay system. Chemokines augmented the migration of the T-leukemia cell lines on fibronectin in the Boyden system in a chemotactic fashion with peak responses at 10 to 50 ng/ml. Thus, the production of chemokines is defective in neoplastic T-lymphocytes. The defective chemokine production does not seem to play any major role for the basic locomotor capacity of the cells but may modulate the responsiveness to exogenous chemokines.

Cytocidal and apoptotic effects of the ClyA protein from Escherichia coli on primary and cultured monocytes and macrophages.

Cytolysin A (ClyA) is a newly discovered cytolytic protein of Escherichia coli K-12 that mediates a hemolytic phenotype. We show here that highly purified ClyA and ClyA-expressing E. coli were cytotoxic and apoptogenic to fresh as well as cultured human and murine monocytes/macrophages.

gammadelta T cells of human early pregnancy decidua: evidence for cytotoxic potency.

The immune compromise in decidua allows a semiallogeneic fetus to survive without impairing the ability of the maternal immune system to fight infections. Cytotoxic mechanisms are likely to be important in this compromise. Using RT-PCR, immunoflow cytometry and immunoelectron microscopy, the cytotoxic potential of isolated human decidual gammadelta T cells was studied. mRNA for perforin (Pf), granzymes A and B, granulysin and Fas ligand (FasL) was simultaneously expressed in decidual gammadelta T cells. Pf and FasL were not expressed on the cell surface. However, the cells constitutively synthesized Pf and stored it in cytolytic granules. Within the granules Pf mainly resided in the granule core formed by Pf-containing microvesicles. Ultrastructurally, three groups of Pf-containing granules were distinguished. They probably represent different stages of granule maturation in a process where Pf-containing microvesicles first attach to the core cortex and then are translocated across the cortex into the core. Presynthesized FasL was also stored in the core and microvesicles of the cytolytic granules. Upon degranulation by ionomycin/Ca(2+) treatment, FasL was rapidly translocated to the cell surface, demonstrating that its surface expression was not controlled by de novo biosynthesis. Thus decidual gammadelta T cells appear to perform Pf- and FasL-mediated cytotoxicity utilizing a common secretory mechanism based on cytolytic granule exocytosis. The first cytochemical visualization of lipids in the cytolytic granules is provided. These intragranular lipids probably wrap up the core and participate in packaging of the cytotoxic proteins as well as in the killing process. An ultrastructural model of a cytolytic granule is presented.

T cell activation in patients with ANCA-associated vasculitis: inefficient immune suppression by therapy.

BACKGROUND AND AIMS: Patients with vasculitic disease and autoantibodies to neutrophil cytoplasmic antigens (ANCA) generally respond to immunosuppressive therapy with a reduction of the inflammation and lowering of the ANCA titre. However, most patients experience relapses, sometimes after years of quiescence. In the present study we addressed the question whether the relapsing nature of this disease could be dependent on an underlying T cell activation. Patients were analyzed at disease onset, in remission while on treatment, and in quiescence. PATIENTS AND METHODS: Blood lymphocyte subsets and the expression of molecules associated with T cell activation were analyzed by flow cytometry and soluble interleukin-2 receptor (sIL2r) levels in serum by ELISA. Three patient categories (la, 1b and 2) were studied and compared with age-matched healthy controls (1a: 16 patients at onset of the disease before therapy, 1b: 10 patients from group 1a, re-analyzed after first remission, 2: 11 other patients in quiescence, 2-10 years after debut). RESULTS: All patient groups, 1a, 1b and 2, showed signs of T cell activation such as reduced CD28 on CD3+ and increased of the early T cell activation marker CD69 on CD3+, as well as of CD38 on CD8+ T cells. The sIL2r levels were significantly raised in all patient categories (la: 4280, 1b: 1844, 2: 2882 ng/ml) compared with the controls (923 ng/ml). CONCLUSION: Patients with ANCA-positive vasculitis show an increased expression of T cell activation markers irrespective of immunosuppressive therapy or disease phase. Such memory cells may form the basis for the remitting course of vasculitides and would be a rational target for new strategies of therapy.

Adhesion molecules (E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) in sera from patients with Staphylococcus aureus bacteraemia with or without endocarditis.

The aim of this prospective study was to evaluate if patients with endocarditis display a more extensive endothelial activation than those with bacteraemia but without endocarditis. Sixty-five patients with blood culture-verified Staphylococcus aureus bacteraemia were included and serum samples collected on admission were analysed by enzyme immunoassays. Elevated serum concentrations of adhesion molecules were found in most of the patients with S. aureus bacteraemia. Patients with endocarditis (n = 15) showed significantly higher serum E-selectin (median 156 ng/ml) and VCAM-1 (median 1745 ng/ml) concentrations compared with those with S. aureus bacteraemia but without endocarditis (80 ng/ml and 1172 ng/ml, respectively; P = 0.01 and P = 0.003). No significant difference was found between the groups concerning ICAM-1 (median 451 ng/ml versus 522 ng/ml). In addition, serum tumour necrosis factor-alpha (TNF-alpha) concentrations were significantly correlated (P < 0.002) to serum levels of E-selectin, ICAM-1 and VCAM-1.

Spectrum of extracellular matrix degrading enzymes in normal and malignant T lymphocytes.

Human T cells produce and release fibronectin degrading neutral serine proteases with a molecular weight of 50 kD, 70-80 kD (doublet) and 95 kD and have a cell associated 400 kD fibronectin degrading enzyme. In addition, human T cells produce proteases with m.w. 50, 70-80 kD and 400 kD which degrade laminin. CD 4+ T lymphocytes from a non-malignant cloned human T cell line produce a 92 kD gelatinase (MMP 9) and malignant T cell lines release, in addition to the 92 kD gelatinase, low amounts of a 72 kD gelatinase (MMP 2). Purification of the enzymatic activities using benzamidine sepharose yields a 50 kD and a 70 kD band of which the 50 kD band has fibronectin degrading capacity. The purified enzymes do not react with monoclonal antibodies to various previously characterized proteolytic enzymes present in T cells. T lymphocytes from a non-malignant cloned human T cell line produce high amounts of the 50 and 70-80 kD proteases directly after stimulation with anti-CD 3 monoclonal antibodies whereafter the production of these enzymes declines with time. The expression of the 400 kD fibronectin-degrading protease is downregulated by crosslinking of alpha 4 beta 1-integrin receptors on T cells using monoclonal antibodies. Thus, T lymphocytes produce several matrix degrading enzymes with multiple substrate specificities. The expression of these enzymes is controlled partly by lymphocyte activation signals or by direct signalling via beta 1-integrins.