Role of neutrophil kinin in infection.
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Humans↗
Biomedical subjects
K D Bhoola
Publications and source records attributed to K D Bhoola.
Proinflammatory role of tissue kallikrein in modulating pain in inflamed joints.
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Arthritis, Psoriatic↗
Identification and functional importance of plasma kallikrein in the synovial fluids of patients with rheumatoid, psoriatic, and osteoarthritis.
OBJECTIVES: To determine and identify, unequivocally, if plasma kallikrein (PK) is present in the synovial fluid of patients with rheumatoid (RA), psoriatic (PA) and osteo (OA) arthritis, and to consider its functional importance in the inflamed joint. METHODS: Therapeutically aspirated synovial fluids (pooled and individual samples, n = 66) were obtained from patients with arthritis. In addition, serum (n = 14) was collected from RA patients, and saliva (n = 10) and urine (n = 10) from normal individuals. Enzymic (amidase) and immunoreactive activities of PK and its precursor, prokallikrein (PPK), were determined. The presence of PK was assessed by incubation with soya bean trypsin inhibitor (SBTI), and by adsorption with anti-PK antibody linked to Sepharose. An enzyme-linked immunosorbant assay (ELISA) for PK was developed for quantitative measurement of total PK in biological fluids. Enhancement of the PK dose-response by RA synovial fluid made it necessary to remove RF from synovial fluids before determination of PK by ELISA. RESULTS: Amidase activity was demonstrated in synovial fluid pools and shown to be inhibited completely by SBTI, and removed by prior treatment with anti-PK Sepharose. Total PK activity (PK + PPK) from individual synovial fluid specimens did not differ significantly between patients with RA (median activity 76 mU/g protein), PA (80 mU/g protein) or OA (60 mU/g protein). Similar results were obtained when active PK alone was measured. No correlation was found between active PK or total PK values and the severity score for individual joints. Most of the measured immunoreactivity was removed by adsorption with anti-PK antibody linked to Sepharose. CONCLUSION: The results support the hypothesis that plasma kallikrein is present in synovial fluid. The enzyme may be important in the pathogenesis of inflamed joints.
Adult↗
A clinicopathological study of collagen sponge as a dural graft in neurosurgery.
There is frequently a need for dural grafts to cover defects resulting from retraction, shrinkage, or excision following neurosurgical procedures. Several materials have been evaluated both experimentally and clinically, and then discarded. Collagen, in its various forms, continues to be an area of intense interest. In this study the authors examined the suitability of collagen sponge to effect dural repair. In a 5-year clinical study 102 collagen sponge implants were examined macroscopically and histologically. Graft encapsulation, neomembrane formation, delayed hemorrhage, and foreign body reactions were not found. The porous nature of the collagen sponge encouraged fibroblastic ingrowth and dural repair. Meningocerebral adhesions were present in 11 patients, all of whom had required significant cortical resection or had pia-arachnoid disruption during the initial surgery. Inflammatory cells were seen only in response to infection. Postoperative cerebrospinal fluid leaks developed in only three of 67 patients who underwent an intradural posterior fossa procedure. In a prospective arm of the study involving 459 patients, the wound infection rate using collagen sponge was 6.1%, which compared favorably (p = 0.67) with the 5.7% rate in a similar group of 637 patients in whom collagen sponge had not been used.
Cerebrospinal Fluid Otorrhea↗
Assembly of contact-phase factors on the surface of the human neutrophil membrane.
H-kininogen (HK), a major factor involved in contact-phase activation, was recently immunolocalized on the external surface of human neutrophils. Experiments were, therefore, designed to consider the question of whether the complete assembly of contact factors occurs on the outer surface of the neutrophil membrane. By immunolocalization techniques, and using specific antibodies directed against the various contact factors, we now demonstrate that plasma prekallikrein (PK), factor XI (FXI), and factor XII (FXII) are present on the exterior face of the human neutrophil. Failure to localize HK, PK, or FXI by monoclonal antibodies directed to their reciprocal binding sites, and displacement of PK/FXI by peptide HK31, which mimics the relevant binding site(s) of HK, suggested that prekallikrein and FXI are anchored to the neutrophil membrane through attachment to the kininogen molecule. Probing of the kinin moiety by a specific antibody showed that kininogen molecules bound to the neutrophil cell membrane contain the kinin sequence, which can be released by plasma kallikrein or by tissue kallikrein. Our results led us to the novel conclusion that neutrophils provide a circulating platform for the components of the contact-phase system.
Cell Membrane↗
Inhibitor regulation of tissue kallikrein activity in the synovial fluid of patients with rheumatoid arthritis.
Tissue kallikrein (TK) and alpha 1-antitrypsin (AT)/TK complexes can be detected in SF from patients with RA if components of the fluids which interfere with the detection of TK are removed. alpha 2-Macroglobulin (alpha 2-M) in SF was demonstrated to contain trapped proteases which were still active in amidase assays. Removal of alpha 2-M from RA SF reduced their amidase activity. However, at least some of the remaining activity was due to TK because it was soya bean trypsin inhibitor resistant and trasylol sensitive and was partly removed by affinity chromatography on anti-TK sepharose. Removal of RF from the fluids reduced the values obtained for TK levels by ELISA. Addition of SF to human urinary kallikrein (HUK) considerably reduced the levels of TK detected suggesting the presence of a TK ELISA inhibitor in the fluids. Removal of components of > 300 kDa from SF markedly reduced the TK ELISA inhibitory activity and increased the values for both the TK and alpha 1-AT/TK levels in fluids as measured by ELISA. It is considered this novel inhibitor does not bind to the active site of TK but rather binds to the site reactive with anti-TK antibodies.
Adult↗
Hyponatremic natriuretic syndrome in tuberculous meningitis: the probable role of atrial natriuretic peptide.
Hyponatremia has been reported in up to one third of patients with intracranial disease and has frequently been associated with tuberculous meningitis, often complicated by hydrocephalus. The lowered plasma sodium levels were previously attributed to the syndrome of inappropriate secretion of antidiuretic hormone. A controlled prospective study of 24 patients with tuberculous meningitis and hydrocephalus was carried out. Analyses of serum electrolytes and cerebrospinal fluid were performed. Plasma and cerebrospinal fluid levels of atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) were measured by radioimmunoassay. Fifteen patients were found to be hyponatremic (plasma sodium < 130 mmol/L) and ANP levels of 12 to 1,488 pg/ml were present (median, 26 pg/ml). The remaining 9 patients had normal plasma sodium values between 130 and 145 mmol/L, and in these, plasma ANP values varied between 12 and 21.7 pg/ml (median, 12 pg/ml). The difference between these two groups was not statistically significant. (Control values from patients undergoing myelography were established to range between 12 and 40 pg/ml; median, 14.4 pg/ml.) ANP levels were undetectable in the cerebrospinal fluid in all. Plasma ADH levels in the hyponatremic group were between 7 and 159 pg/ml (median, 40 pg/ml). In the normonatremic group, plasma ADH levels of 25 to 250 pg/ml (median, 29 pg/ml) were obtained. (The controls ranged between 3.6 and 35 pg/ml; median, 10.4 pg/ml). In the hyponatremic group, there was a moderate negative correlation (r = -0.683) between plasma ANP and plasma sodium (P = 0.02). No correlation between plasma ADH and plasma sodium was found (r = -0.168; P = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS)
Atrial Natriuretic Factor↗
Cellular localization of atrial natriuretic peptide and tissue kallikrein in the human hypothalamus.
In the kidney, renal atrial natriuretic peptide (ANP) is considered to play an important role in water and salt homeostasis. Immunoreactive ANP in the brain of lower invertebrates, such as the rat, has been shown to be localized in the hypothalamus and septum. Several studies have investigated the possibility of a regulatory system in the brain similar to that of the kidney. Since neuronal function is acutely sensitive to disturbances of the intracranial water and salt balance we have attempted to immunolocalize ANP-containing cells in the normal human hypothalamus, using a polyclonal antiserum specific to ANP. Also, we have observed tissue kallikrein (TK), using a polyclonal antiserum specific to TK, in the same areas as ANP. A regulatory role for TK on prolactin has been suggested as the rationale for the co-localization of these two hormones in human prolactinomas. Therefore, it could be suggested that TK plays a similar role in the processing of precursor ANP in the brain. It is contemplated to examine the status of these peptides in patients with cerebral oedema.
Atrial Natriuretic Factor↗
Localization of immunoreactive tissue kallikrein in the seromucous glands of the human and guinea-pig respiratory tree.
An immunocytochemical study focused on the cellular localization of tissue kallikrein along the human and guinea-pig respiratory tracts is reported. A strong immunoreactivity for tissue kallikrein was observed in the seromucous glands of the nasal mucosa, trachea, and bronchi. In these glands, the immunostaining was restricted to the serous component of the acinus whereas mucous cells showed no staining. Since no immunoreactivity to kininogen was observed in any of the tissue constituents of the human and guinea-pig respiratory tree, transudation of the substrate from plasma was considered to be the preferred mode of delivery of the kininogen into the bronchopulmonary interstitium and lumen. Our results provide morphological evidence for the well documented presence of tissue kallikrein in bronchial lavage fluids and support the hypothesis that kinins may be one of the more important mediators involved during acute episodes of asthma and rhinitis.
Animals↗
Immunovisualization of high (HK) and low (LK) molecular weight kininogens on isolated human neutrophils.
An immunocytochemical study was performed to examine the cellular localization and the subcellular distribution of kininogens in human blood cells. Kininogens were visualised using the immunogold-silver staining method and confocal scanning laser microscopy. We confirmed the existence of high molecular weight kininogen in human neutrophils and describe for the first time the presence of low molecular weight kininogen on these cells. Both high and low molecular weight kininogens were restricted to the neutrophils where they localized as clusters of immunogold particles on the cell membrane. No labeling was observed intracellularly in organelles such as mitochondria, endoplasmic reticulum, and azurophilic or specific granules after permeabilization of the neutrophils with Triton X-100, a procedure that permitted the visualization of elastase in the azurophilic granules. Clusters of high molecular weight kininogen molecules attached to the neutrophil surface could serve as receptors for plasma kallikrein and/or be the source of substrate for a discrete and circumscribed formation of kinins that may in turn facilitate the local diapedesis of neutrophils and the transudation of plasma constituents during acute inflammation.
Antibodies, Monoclonal↗
Metabolism and characterisation of kinins and Hoe 140 (kinin antagonist) in the synovial fluid of patients with inflammatory joint diseases.
Methods have been optimised for the collection of synovial fluid and the chromatographic separation of individual kinins (bradykinin and kallidin) in the fluid by HPLC. In addition, the stability of the kinin antagonist, Hoe 140, in synovial fluid was compared with that of synthetic bradykinin. Although bradykinin was completely degraded after incubation for only 6 h in pooled synovial fluid obtained from patients with rheumatoid arthritis, Hoe 140 was stable for as long as 2 weeks under the same conditions. These studies will provide quantitative information regarding levels of kinins in inflamed joints and an insight into the therapeutic potential of kinin antagonists.
Anti-Inflammatory Agents, Non-Steroidal↗
Immunovisualisation of plasma prekallikrein and H-kininogen on human neutrophils and in human hepatocytes.
Both plasma prekallikrein and H-kininogen were immunolocalised in human hepatocytes by the use of immunocytochemical techniques in conjunction with the confocal optical scanning microscopy. In contrast, both proteins were demonstrated on the external surface of human blood neutrophils. However, detection of H-kininogen on non-fixed but not on fixed neutrophils with the anti-domain 6 antibody (directed at the prekallikrein binding site on H-kininogen), suggested that access to the epitope was blocked by the presence of the bound plasma prekallikrein. Therefore, we prepose that H-kininogen provides the binding site for plasma prekallikrein on circulating neutrophils.
Adult↗
Cellular localization of human kininogens.
An immunocytochemical screening using polyclonal and monoclonal antikininogen antibodies was performed in various human tissues including blood cells. By comparing the spatial relationship between the cellular localizations of tissue kallikrein and kininogens it was evident that in some tissues both enzyme and substrate were present establishing a close anatomical relationship whereas in others only one of the components could be detected. This pattern of distribution suggests that within various tissues (cells) the major function of either tissue kallikrein (kininogenase, processing enzyme) or kininogen (kinin precursor, cysteine protease inhibitor, kallikrein acceptor molecule) could be different and probably specific to each cell type.
Amino Acid Sequence↗
Kinins--key mediators in inflammatory arthritis?
Recent evidence suggests an important role for kinins in the generation of pain, swelling and the cellular damage associated with inflammatory joint disease. Kinins are considered to be pro-inflammatory peptides for a variety of reasons. They stimulate c fibres in the synovium to cause pain and increase extravasation of fluid to produce swelling. Kinins possess the capacity to release neurotransmitters (substance P, acetylcholine) and a second wave of mediators (interleukin-1, tumour necrosis factor, interleukin-8, prostaglandins, leukotrienes). The steady levels and turnover of kinins is regulated by formation (enzymic action of kininogenases on endogenous substrates called kininogens) and by metabolism (kininases, peptidases that hydrolyse kinins). These components of the kinin system can enter the synovial joint space either by transudation from the plasma or from degranulating neutrophils chemotactically attracted into the synovium from which they migrate into the synovial fluid. If kinins are involved, one would expect neutrophil derived mediators of the system to dominate in rheumatoid arthritis and psoriatic arthritis and plasma derived products to be more important in osteoarthritis and gout. But, the question whether any of the functions attributed to each component of the system can be considered to be a primary factor in the cellular pathology of inflamed joints remains to be established. Future investigations, including therapeutic trials with kinin antagonists and kallikrein inhibitors, will need to address the differential role of the kallikreins and kinins in the different types of synovitis, on symptoms of inflammation and on any remedial effects on the progression of tissue damage within the joint.
Amino Acid Sequence↗
Bioregulatory role of the kallikrein-kinin system in the normal pituitary gland and its tumours.
Tissue kallikrein, a serine protease, is present in the prolactin-secreting cells of the normal anterior pituitary gland and pituitary adenomas. It is mainly located in the Golgi apparatus, but is also present in secretory granules. There is a distinct sexual dimorphism, with amount of tissue kallikrein being greater in anterior pituitary tissue from female rats. The intracellular levels of tissue kallikrein are increased by estradiol and in pituitary tumours, and decreased by ovariectomy, dopamine and its agonists. There is preliminary in vitro evidence that tissue kallikrein may be involved in the intracellular processing of the prolactin molecule before secretion. Tissue kallikrein synthesizes kinins which are present in the anterior pituitary and are capable of stimulating prolactin and growth hormone secretion by activating the phosphoinositide second messenger system. Prolactin physiology is uniquely linked to the kallikrein-kinin system in the normal pituitary and its tumours. Tissue kallikrein may have an important role in the pathophysiology of prolactin-secreting pituitary adenomas.
Adenoma↗
Tissue kallikrein is associated with prolactin-secreting cells within human growth hormone-secreting adenomas.
Tissue kallikrein is a serine protease which may be involved in the intracellular processing of prolactin in the anterior pituitary gland. The expression of tissue kallikrein, in the rat, is promoted by oestrogen and inhibited by dopamine. Human and rat prolactinomas contain markedly increased amounts of tissue kallikrein; this is comparatively reduced if patients are pretreated with the dopamine agonist, bromocriptine, before surgery. Some GH-secreting adenomas are mixed and also contain prolactin-secreting cells. We therefore investigated 27 GH-immunostaining human pituitary adenomas for the presence of immunoreactive tissue kallikrein. Sixteen of the adenomas had positive immunostaining for prolactin; eight of these patients had associated clinical hyperprolactinaemia before the tumour was removed. Tissue kallikrein immunoreactivity was found in ten adenomas, all of which also had prolactin immunopositivity. There was a close relationship between the percentage of cells staining for prolactin and tissue kallikrein but not for GH. A further eight adenomas had patchy positivity, i.e. less than 1% of cells immunostained for tissue kallikrein and six of these also had some prolactin-staining cells. Nine out of eleven purely GH-staining adenomas had no tissue kallikrein immunopositivity, the remaining two showing patchy staining. A review of bromocriptine responsiveness, as assessed by mean GH hormone levels during oral glucose tolerance tests before and after therapy was commenced, indicated that patients with adenomas which stained for prolactin and tissue kallikrein were more likely to respond to bromocriptine than those which failed to do so.
Adenoma↗
Mediators of joint swelling and damage in rheumatoid arthritis and pristane induced arthritis.
Joint swelling and tenderness in rheumatoid arthritis (RA) probably result from IgG aggregates activating complement with the consequent attraction of polymorphonuclear leucocytes (PMNs) and the liberation of their granule enzymes such as kininogenases. By contrast IL-1 and TNF are the major stimulants of cartilage and bone loss although other agents contribute. The fundamental drive for the production of these mediators is unknown but a role for heat shock proteins is suggested from work on pristane induced arthritis.
Animals↗
Bioregulation of kinins: kallikreins, kininogens, and kininases.
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Animals↗