Complement and function of neutrophils in chronic inflammatory bowel disease.
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Colitis, Ulcerative↗
Biomedical subjects
J Elmgreen
Publications and source records attributed to J Elmgreen.
Demonstration of circulating immune complexes by the indirect leucocyte phagocytosis test in chronic inflammatory bowel disease. Relation to results of a standard complement consumption assay.
Circulating immune complexes were studied in untreated Crohn's disease (CD) and ulcerative colitis (UC) by leucocyte phagocytosis. Neutrophils from normal donors took up large immunoglobulin-containing inclusions from 14 of 15 CD sera, 3 of 15 UC sera (p less than 0.002) and from none of 15 reference sera from healthy volunteers (p less than 0.002). In contrast, inclusions could not be demonstrated on direct microscopic investigation. Our study confirms the presence of circulating immune complexes in Crohn's disease. Predominance of IgG-containing complexes in this condition is consistent with a mucosal origin. Discrepant results obtained by direct examination and by incubation of sera from patients with normal test neutrophils suggest a defective immune complex phagocytosis in CD. In consistency with this possibility, control experiments revealed a markedly decreased complex uptake by neutrophils of CD patients in vitro.
Antigen-Antibody Complex↗
Progressive muscular dystrophy in Denmark. Natural history, prevalence and incidence.
Prevalence of progressive muscular dystrophy in 1965 and incidence in Denmark for the period 1965 to 1975 was studied by collection of data from hospital departments, nursery homes and general practitioners. This material was supplemented with information from death certificates and disablement pension records. Total patient group included 445 patients with progressive muscular dystrophy alive January 1st 1965. Prevalence was 69.4 per 10(6) male inhabitants in the Duchenne type, whereas the prevalences in the limb-girdle and facioscapulohumeral types were 36.5 and 18.6 per 10(6) inhabitants, respectively. Incidence was 222 per 10(6) male newborns in the Duchenne type, 66 and 26 per 10(6) newborns for the limb-girdle and the facioscapulohumeral types, respectively. Figures for the Duchenne type are in agreement with previous results. Both prevalence and incidence rates for the limb-girdle and the facioscapulohumeral types exceed published figures by a factor 3 to 6. These high Danish rates seem to reflect the true prevalence and incidence in the less serious types of progressive muscular dystrophy, probably because the Danish health system with free medical care and easy access to specialized hospital departments makes it possible to identify all cases of progressive muscular dystrophy.
Adolescent↗
Neutrophil recruitment in skin window chambers--activation by complement.
Complement was studied in skin window chambers, a human model of neutrophil recruitment in acute aseptic inflammation. Autologous plasma activated by the alternative pathway served as attractant; control chambers were filled with a balanced salt solution or with non-activated plasma samples. Neutrophil accumulation during a 24-hour period was consistently enhanced by activated complement in all of 15 healthy volunteers. Control chambers showed negligible cell counts. Reference assays revealed 1) consumption of the centrally placed complement component, C3, 2) generation of chemotactic activity as assessed in Boyden chambers by the standard complement activation procedure. Simultaneously obtained responses to activated complement in skin window chambers and in the Boyden assay of chemotaxis showed a highly significant, positive correlation. Our results demonstrate that the biological capacity of complement includes stimulation of neutrophil migration during simulated in vivo conditions and thus extends previous observations in animals.
Chemotaxis, Leukocyte↗
Subnormal sensitivity of neutrophils to complement split product C5a in rheumatoid arthritis: relation to complement catabolism and disease extent.
The capacity of circulating neutrophils for activation by complement was studied in outpatients with classical or definite rheumatoid arthritis during treatment with dextropropoxyphene only. Analysis of dose-response in the Boyden chamber assay of chemotaxis showed that sensitivity to the potent, complement derived anaphylatoxin, C5a, was markedly decreased, especially in those patients with few joints involved. In contrast, peak response to C5a was within the normal range. Increased complement 3c split products in plasma of the patients suggested involvement of complement cascade reactions. Subnormal sensitivity of neutrophils to phlogistic mediators released by complement may tend to limit their recruitment and potentially tissue destroying secretion locally in rheumatoid arthritis.
Adult↗
Familial occurrence of complement dysfunction in Crohn's disease: correlation with intestinal symptoms and hypercatabolism of complement.
Complement was studied in Crohn's disease probands with early onset and in their first degree relatives. Controls included 24 healthy volunteers and 24 patients with ulcerative colitis or peptic ulcers. Subnormal generation of chemotactic activity by the alternative pathway was shown in eight of 21 probands and in six of 33 relatives, a frequency in both groups significantly different from controls (p less than 0.005), with a strong connection between findings in patients and relatives. As previously shown in patients with Crohn's disease, the subnormal generation was related to decreased utilisation of complement C3 in relatives. Raised levels of circulating complement C3c split products suggested complement involvement in Crohn's disease probands. In contrast, plasma C3c was normal in all relatives, and none of the six cases with complement dysfunction had gastrointestinal symptoms or a history of inflammatory bowel disease. Our data suggest, that complement abnormality seen in Crohn's disease patients does not simply reflect mucosal inflammation or hypercatabolism of complement.
Adolescent↗
Defective modulation of complement in Crohn's disease. C3b opsonization of zymosan by the alternative pathway.
Opsonization of zymosan by plasma complement was studied in 12 consecutive patients with untreated, well-established Crohn's disease and in 12 healthy volunteers. Binding of C3b to zymosan was markedly increased in patients with Crohn's disease during the first 30 min of the alternative pathway reaction, whereas consumption of the native C3 protein was within the normal range in all patients. Our results are consistent with a decreased capacity for degradation of activated C3,C3b by the I-H factor inactivator system. This immunologic abnormality may contribute to a chronic activation of the complement sequence, previously demonstrated in Crohn's disease, and to a release of split products of inflammation-promoting character.
Complement C3b↗
In vitro labeling of human polymorphonuclear leukocytes with 99mTc.
Preliminary experience with 99mTc labeling of isolated polymorphonuclear leukocytes is reported. Leukocytes efficiently purified from 100 ml peripheral blood were labeled in vitro with 99mTc after pretreatment with small amounts of a stannous agent to reduce pertechnetate. A labeling yield of 1.3 mCi equivalent to 12.5% of the added dose of 99mTc and a cell binding efficiency of more than 90% was achieved under sterile conditions. Viability assays showed no influence of the labeling procedure on cell function. The technique may prove a valuable alternative for assessment of local leukocyte accumulation by scintigraphy.
Cell Survival↗
Polymorphism of complement C3 in chronic inflammatory bowel disease. Predominance of the C3F gene in Crohn's disease.
Polymorphism of the third component of complement (C3), occupying a key position in cascade reactions, was investigated in 125 consecutive outpatients, 53 with Crohn's disease and 72 with ulcerative colitis. A sample of 1378 randomly selected healthy volunteers of Danish origin served as controls. Occurrence of the F and FS phenotype of C3 (C3F and C3FS ) was increased in the group of Crohn's disease patients (chi 2 = 2.80, p less than 0.05, one-tailed test) and in a subgroup of Crohn patients with the gastrointestinal disease process confined to ileum (chi 2 = 6.91, p less than 0.01). C3 phenotype distribution was unaffected in ulcerative colitis. Only S and F alleles of C3 ( C3S and C3F) were recognized and C3F frequencies were 0.33 in Crohn patients with small bowel disease, 0.23 in all Crohn patients, 0.18 in ulcerative colitis patients and 0.17 in healthy volunteers. The results are compatible with a positive association of the C3F gene and Crohn's disease located in the small bowel.
Alleles↗
Type I allergy to normal cellular constituents in chronic inflammatory bowel disease? Results from basophil histamine release test compared with total IgE and antinuclear antibodies.
The possibility of autoimmune type I reactions to cellular constituents was investigated in 22 patients with ulcerative colitis, 12 with Crohn's disease, and in 22 healthy volunteers. Nuclear components and colon mucosa fragments were tested as potential antigens by the basophil histamine release technique. One of 12 patients with ulcerative colitis responded to sonicated leukocyte nuclei and one of 12 patients with Crohn's disease responded to both nuclei and RNA. Increased serum levels of total IgE and antinuclear antibodies of IgE class were found in one and three of the 24 patients, respectively. Histamine release caused by colon mucosa fragments was not observed in a separate study consisting of 10 ulcerative colitis patients and 10 healthy volunteers. Autoimmune type I allergy to cellular constituents does not seem to be of significance for chronic inflammatory bowel disease and thus could not explain the involvement of tissue mast cells and eosinophils in this condition.
Adult↗
Subnormal activation of phagocytes by complement in chronic inflammatory bowel disease? Neutrophil chemotaxis to complement split product C5a.
The capacity of circulating phagocytes for activation by complement was investigated in consecutive, untreated cases of chronic inflammatory bowel disease. The major complement derived chemotactic factor, C5a, served as chemoattractant in dose response studies of neutrophil chemotaxis. A similar, significantly decreased sensitivity and peak response was revealed in patients with Crohn's disease and ulcerative colitis. This subnormal function of neutrophils could be shown even in cases of complete clinical remission. Chemotactic response to casein and spontaneous motility was within the normal range showing an unaffected basic cell function of neutrophils in the patients. The study shows a dysfunction of phagocytic cells, related to potentially important phlogistic mediators, in chronic inflammatory bowel disease.
Adult↗
Hypercatabolism of complement in Crohn's disease--assessment of circulating C3c.
Split products from the main complement component 3 (C3) were investigated in untreated outpatients, 20 with Crohn's disease and 20 with ulcerative colitis. The median plasma concentration of c split product of C3 (C3c) in normals was 2 mg X 1(-1), in patients with Crohn's disease 20 mg X 1(-1) and in patients with ulcerative colitis 3 mg X 1(-1). This tenfold increase in C3c was significant at the 0.005-level. Plasma C3c exceeded the reference interval in two patients with ulcerative colitis. C3c levels did not correlate to the activity of the disease or to the occurrence of the C3 phenotypes S, FS and F. Substantially elevated plasma C3c in Crohn's disease suggests hypercatabolism of C3, that is, involvement of complement reactions. Further studies are needed to reveal the site of cascade activation and to define the role of complement for the pathogenesis of the disease.
Colitis, Ulcerative↗
Defective release of C5a related chemo-attractant activity from complement in Crohn's disease.
Complement was studied in 20 untreated cases of Crohn's disease and in 20 healthy volunteers by an in vitro activation of the cascade reaction. Total haemolytic complement was normal in all patients. In contrast, activation of the alternative pathway lead to a decreased release of C5a related chemo-attractant activity together with a subnormal utilisation of the main complement component C3. This abnormality of complement function was not related to the activity of the disease, site of involvement or to disease duration. The results suggest that an inadequate stimulation of important neutrophil functions may result when bacterial lipopolysaccharides and other macromolecules activating the alternative pathway penetrate the gut mucosa. A delayed clearance from the tissue of such foreign material could be a further pathogenic factor in Crohn's disease leading to granulomatous inflammation by a foreign body reaction.
Chemotaxis, Leukocyte↗
Granulocyte specific antinuclear antibodies in ulcerative colitis. Aid in differential diagnosis of inflammatory bowel disease.
40 patients with ulcerative colitis (UC) and 35 patients with Crohn's disease (CD) were studied for the occurrence of granulocyte specific (GS-) antinuclear antibodies (ANA) and organ-non-specific (ON-) ANA. The predominant immunoglobulin class of GS-ANA in UC was IgG, present in 25% of the patients, but only in 3% of the patients with CD (p less than 0.02). ON-ANA were are in both groups and did not allow discrimination between these. Both GS-ANA and ON-ANA lacked complement-fixing properties. No relation was found between the types or titres of IgG ANA and sex, age, duration, disease activity or localization in the two groups of patients. The significance of our serologic observations in relation to these disease parameters has to be determined n larger prospective studies.
Adolescent↗
The chemotactic function of neutrophils in ulcerative colitis.
Neutrophil chemotactic function was investigated in 30 patients with ulcerative colitis (UC) in an active (no. = 15) or an inactive (no. = 15) stage. Peripheral blood neutrophils from active cases had a significantly decreased stimulated migration in modified Boyden chambers. Simultaneously done investigations of neutrophil migration into skin window chambers showed normal results in both active and inactive cases of UC. Thus, the defective chemotaxis during in vitro conditions was not reflected in a quantifiable neutrophil dysfunction in experimental acute inflammation.
Adolescent↗
Varying involvement of peripheral granulocytes in the clonal abnormality - 7 in bone marrow cells in preleukemia secondary to treatment of other malignant tumors: cytogenetic results compared with results of flow cytometric DNA analysis and neutrophil chemotaxis.
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Acute Disease↗
Effect of short-term and long-term treatment with metoprolol on renal blood flow and glomerular filtration rate in hypertensive patients with a normal kidney function.
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Adult↗
Lack of adrenergic influence on renin release after furosemide in normal man.
The role of the sympathetic nervous system in furosemide-induced renin release was investigated in six normal subjects. After intravenous administration of furosemide, plasma renin concentrations increased more than two-fold within 15 min. Neither replacement of urinary fluid loss by intravenous infusion of saline nor pharmacological beta-blockade with d,1-propranolol changed the renin response to furosemide. The activity of the sympathetic nervous system, as estimated by measurement of plasma catecholamine concentrations, remained at the reference level after furosemide. It is concluded that the sympathetic nervous system is not involved in renin release after intravenous administration of furosemide.
Adult↗