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At least 217 records · Page 12Linked to original sources
PubMed1985

Structure and function of human C5a anaphylatoxin. Selective modification of tyrosine 23 alters biological activity but not antigenicity.

Reaction of either human C5a or its des-Arg74 derivative (des-Arg74-C5a) with tetranitromethane under nondenaturing conditions results in selective nitration of only 1 of the 2 tyrosine residues found in these glycopolypeptides. This reactive tyrosyl residue was identified as that found in position 23 of the sequence. Nitrotyrosyl23-C5a and -des-Arg74-C5a were separated from their respective unmodified precursors by cation-exchange fast protein liquid chromatography. These purified derivatives served as reagents for the subsequent preparation of both aminotyrosyl23-C5a and -des-Arg74-C5a as well as photoreactive analogs of C5a. Radioimmunoassays performed with C5a derivatives serving as competing ligands and a murine antihuman C5a monoclonal antibody employed as first antibody demonstrated that selective modification of tyrosine23 did not produce a detectible alteration in the antigenic properties of C5a. By contrast, either nitro- or aminotyrosyl23-C5a was approximately 3-fold less active than native C5a in both bioassays and competitive ligand-receptor binding assays. Additionally, photoreactive derivatives prepared by coupling either N-succinimidyl-6-(4'-azido-2'-nitrophenylamino)-hexanoate or p-nitrophenyl-2-diazo-3,3,3-trifluoropropionate to aminotyrosyl23-C5a at pH 5.0 failed to interact with the neutrophil C5a receptor. These observations suggest that the tyrosyl23 residue of C5a may participate importantly in the binding interactions of this chemotactic factor and its granulocyte receptor.

Affinity Labels↗
PubMed1989

Human erythrocytes inhibit complement-mediated solubilization of immune complexes.

Incubation of precipitable immune complexes (IC) with fresh human serum or guinea pig serum resulted in solubilization of IC. When packed human E were added to human serum or guinea pig serum, binding of IC to the E occurred and IC solubilization was significantly inhibited. By contrast, SRBC did not bind IC nor inhibit IC solubilization. Because IC binding to human E is mediated by CR type 1 (CR1) we evaluated whether CR1 was responsible for the inhibition of IC solubilization. Human E were treated with trypsin or anti-CR1 mAb. Both treatments abrogated IC binding to human E but did not affect the ability of the human E to inhibit IC solubilization. Human E inhibited C activation by IC. Thus, incubation of IC in human serum caused significant activation of C3 and C5, but not C4. However, when IC were incubated in whole blood or with isolated human E and serum, C3 activation by IC was inhibited significantly. In addition, we demonstrated that the C3b generated during C activation by IC deposited on both IC and human E. Thus, human E may compete for nascent C3 generated during C activation by IC. In conclusion, human E inhibit both complement-mediated solubilization of IC and C activation by IC.

Antigen-Antibody Complex↗
PubMedDate not supplied

[The reactivity of pulmonary and hepatic macrophages in normal and prestimulated animals].

The rate of blood clearing of colloidal carbon increased two-fold as compared to the controls 5 days after prodigiosin injection. This was attended by intensified recruitment of macrophages into the alveoli and increase in the number of phagocytizing macrophages in the interstitium of the lungs by 1.5 times above normal. After administration of zymosan granules, the rate of colloid carbon clearance increased 1.5-fold in 5 days and 2.5-fold on the 9th day; the recruitment of macrophages into the alveoli and the number of phagocytizing macrophages in the interstitium of the lungs increased two-fold. At the same time, granuloma-type mononuclear infiltrates formed in the lungs and liver. Prodigiosin injection increases the rate of blood clearance 1.2-fold in animals stimulated by zymosan granules, while the volume of mononuclear infiltration, which acquires a diffuse character, increases 2.5-fold as compared to the value in zymosan stimulated animals. The effects of phagocyte reconciliation may be directly related to exacerbations of chronic inflammatory diseases of different localization.

Animals↗
PubMed1987

Neutrophil chemotactic activity produced by normal and activated human bronchoalveolar lavage cells.

Activated macrophages can secrete a number of mediators that can attract inflammatory cells and enhance secretion of phlogistic substances from these cells. The ultimate effect of activated bronchoalveolar lavage (BAL) cells may be fibrotic lung injury. Inasmuch as pulmonary sarcoidosis is a disease associated with spontaneous activation of macrophages and lymphocytes among BAL cells, cells obtained from patients with sarcoidosis were compared with normal cells. We report that adherent BAL cells in culture from patients with sarcoidosis (n = 21) release during a resting period in vitro more chemotactic activity for neutrophils (PMNs) than do BAL cells from normal individuals (n = 14). After density fractionation of the respiratory cells by albumin gradient, cells from high-density fractions in the group with sarcoidosis secrete more chemotactic activity for neutrophils than cells from less dense fractions. The PMN chemotactic activity spontaneously released in vitro by BAL cells from patients with sarcoidosis correlates with the percentage of PMNs recovered by BAL. Immunochemical bioassay and high-performance liquid chromatographic (HPLC) analysis of BAL cell supernatants revealed a complex pattern of chemotactic factors to be present. Generally, three peaks of chemotactic activity were noted on HPLC 1-60 separations at greater than 20 kd, 8 to 10 kd, and less than 1 kd apparent molecular weights. Significantly, interleukin-1 was present in these supernatants, whereas complement components and leukotriene B4 were absent. Sarcoid BAL cells, principally alveolar macrophages, are activated in vivo as manifested by spontaneous secretion of chemotactic factors for PMNs in vitro. Interleukin-1 and other less well characterized molecules were detected. The presence of PMNs among the lavage cells of some patients with sarcoidosis appears to be an in vivo biologic correlate of this activation. These data provide additional criteria of BAL cell activation in patients with pulmonary sarcoidosis and provide further evidence concerning factors that attract inflammatory cells into the lung.

Bronchoalveolar Lavage Fluid↗
PubMed1987

Complement activation and vascular injury in systemic lupus erythematosus.

The deposition of immune complexes within blood vessel walls results in the potential for complement activation and the release of chemotactic factors, such as fragments of C5 (C5fr). The generation of C5fr results in the intravascular aggregation of neutrophils with subsequent leukostatic occlusion of the pulmonary arterioles. The generation of C5fr may contribute to the pathogenesis of adult respiratory distress syndrome and other diseases. Studies were undertaken to determine the role of circulating complement derived peptides and intravascular neutrophil activation in systemic lupus erythematosus.

Antigen-Antibody Complex↗
PubMed1987

Non-IgE antibody mediated mechanisms in food allergy.

Food sensitivity or intolerance is not necessarily based on the Type I allergic reaction. Non-IgE antibody reactions, complement-dependent reactions, enzyme deficiencies such as lactase and non-immunologic histamine release (such as with some sea foods) have been described. Even the detection of specific antibodies on their own does not necessarily indicate that a given symptom is due to that antibody. Food allergy nevertheless exists. It is important that those observers fortunate enough to see many cases document their observations carefully and eventually publish them for the education of their less fortunate colleagues. Is food allergy more common in infants and young children? What happens as they grow older? How often is atopic eczema due to food allergy? Why are some foods more likely to be implicated than others? Does a negative RAST result eliminate the diagnosis or a positive one confirm it? Until the answers to these and other questions are known, the mainstay of diagnosis will be the history, and that of treatment will be the elimination diet.

Animals↗
PubMed1986

C5a receptor modulation on neutrophils and monocytes from chronic hemodialysis and peritoneal dialysis patients.

Chronic renal failure patients have an increased risk for infection which may partially be due to altered chemotactic ability of their white blood cells. This study was designed to evaluate chemotactic factor and Fc receptor expression on neutrophils (PMN) and monocytes from chronic renal failure patients on hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Analysis of these receptors was performed using flow cytometry and fluorescent chemotactic factors (C5a, f-Met-Leu-Phe-Lys [fMLPL] and casein) and heat-aggregated human IgG. Peripheral blood PMN and monocytes obtained from 14 HD patients (in the predialysis period) and 14 CAPD patients were analyzed for their ability to bind each of the fluoresceinated ligands. PMN and monocytes from both patient groups had a significant reduction in their ability to bind C5a. The average percentage (+/- s.e.m.) of PMN that bound C5a was 93.9 +/- 1.1 for the controls, 72.9 +/- 3.8 for HD patients, and 79.3 +/- 4.0 for CAPD patients. Similar results were obtained with monocytes with 69.7 +/- 1.9% for controls, 54.6 +/- 4.5% for HD patients, and 31.0 +/- 4.5% for CAPD patients. These differences in C5a binding were also reflected in the average intensity of fluorescence. There was no significant difference in the percentage or fluorescence intensity of PMN or monocytes that bound casein or aggregated IgG when either group of dialysis patients was compared to the control values. Binding of fMLPL by PMN and monocytes from the HD patients and PMN from the CAPD patients were similar to control values but the binding of fMLPL by monocytes from CAPD patients was significantly suppressed (p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Complement C3↗