Journal of Immunology
1550-6606
0022-1767
Mỹ
Cơ quản chủ quản: American Association of Immunologists , AMER ASSOC IMMUNOLOGISTS
Lĩnh vực:
Immunology and AllergyImmunology
Các bài báo tiêu biểu
Regulation of aminopeptidase-N (CD13) and Fc epsilon RIIb (CD23) expression by IL-4 depends on the stage of maturation of monocytes/macrophages. Abstract
IL-4 has multiple biologic activities and it has been shown to have effects on B and T lymphocytes, mast cells, NK cells, and monocytes. We studied the influence of IL-4 on the expression of cell membrane determinants, in particular aminopeptidase-N (CD13) and Fc epsilon RIIb (CD23), on human peripheral blood monocytes. We compared the response of monocytes with the response of human alveolar macrophages and monocytic cell lines (U937 and THP1), as mature and more immature representatives of the mononuclear phagocyte system, respectively. A dose-dependent increase of the expression of CD13 Ag was observed when monocytes were cultured with IL-4. Kinetic analyses revealed that this induction was maximal after 2 to 3 days of culture and resembled the kinetics of IL-4-induced expression of Fc epsilon RIIb on monocytes. This IL-4-induced increase was absent when monocytes were cultured with IL-4 and an anti-IL-4 antiserum. Concomitantly, an IL-4-induced increase in leucine-aminopeptidase activity could be observed. Northern blot analysis showed that incubation of monocytes with IL-4 induced a marked increase in CD13 mRNA. Alveolar macrophages also exhibited an increase in CD13 Ag expression when exposed to IL-4. Surprisingly, IL-4 was unable to induce expression of Fc epsilon RIIb on alveolar macrophages. U937 and THP1 cells did not show an induction of CD13 Ag when cultured in the presence of IL-4. However, IL-4 did induce the expression of Fc epsilon RIIb on both cell lines, suggesting the presence of functional IL-4R. Our data demonstrate that IL-4 increases the expression of CD13 Ag on monocytes. This IL-4-induced increase can also be observed in more mature monocytic cells such as alveolar macrophages, but is absent in immature cells such as U937 or THP1 cells. This is functionally accompanied by an increase in leucine-aminopeptidase activity and may be part of the general activation of monocytes/macrophages by IL-4. In conclusion, the data suggest that IL-4 responsiveness, in particular the induction of CD13 Ag and Fc epsilon RIIb expression, may be dependent on the stage of maturation of monocytes/macrophages.
Tập 149 Số 4 - Trang 1395-1401 - 1992
Defining the Origins and Evolution of the Chemokine/Chemokine Receptor System Abstract
The chemokine system has a critical role in mammalian immunity, but the evolutionary history of chemokines and chemokine receptors are ill-defined. We used comparative whole genome analysis of fruit fly, sea urchin, sea squirt, pufferfish, zebrafish, frog, and chicken to identify chemokines and chemokine receptors in each species. We report 127 chemokine and 70 chemokine receptor genes in the 7 species, with zebrafish having the most chemokines, 63, and chemokine receptors, 24. Fruit fly, sea urchin, and sea squirt have no identifiable chemokines or chemokine receptors. This study represents the most comprehensive analysis of the chemokine system to date and the only complete characterization of chemokine systems outside of mouse and human. We establish a clear evolutionary model of the chemokine system and trace the origin of the chemokine system to ∼650 million years ago, identifying critical steps in their evolution and demonstrating a more extensive chemokine system in fish than previously thought.
Tập 176 Số 1 - Trang 401-415 - 2006
The Heterogeneity of Combining Sites of Antibodies as Determined by Specific Immunoadsorbents Summary
Anti-Xp antibodies labeled with radioactive iodine were fractionated by adsorption on the Xp-adsorbent and subsequent successive elutions either with increasing concentrations of p-nitrobenzoate (fractions I, III and V) or with single concentrations of o-, m- and p-nitrobenzoates (fractions O, M and P).
Eluted antibodies were characterized by adsorption on three different immunoadsorbents containing the p-azobenzoate (Xp), p-azo-o-chlorobenzoate (o-ClXp) or p(p′-azophenylazo)-benzoate groups (X′) and elution at various concentrations of each of six haptens, benzoate, p-nitrobenzoate, m-nitrobenzoate, p-aminobenzoate, o-chlorobenzoate and o-nitrobenzoate. The effectiveness of each hapten to elute antibody from the adsorbent was expressed as the logarithm of the reciprocal of hapten concentration required to elute 50% of antibody adsorbed (pEC50).
The relative values of pEC50 between haptens differed from antibody fraction to antibody fraction, indicating that there is a difference of specificity among the antibody fractions. However, the order of pEC50 values of various haptens with each adsorbent was p-nitro- > m-nitro- > p-amino- = unsubstituted > o-chloro- > o-nitrobenzoates for all the antibody fractions as well as for the original unfractionated antibody.
The order of pEC50 values of various immunoadsorbents was X′ > o-ClXp > Xp for the original unfractionated antibody fraction and fraction III, V, M and P, X′ > o-ClXp = Xp for fraction I and X′ = o-ClXp = Xp for fraction O. This reflects the difference among the antibody fractions with respect to the abilities to accommodate the o-substituent group and with respect to the extent of the contribution of the protein portion surrounding the haptenic group to their combination with the immunoadsorbent.
Tập 95 Số 6 - Trang 991-1001 - 1965
Studies on the Combining Sites of the Protein Antigen Silk Fibroin Summary
The octapeptide Gly(Gly3,Ala3)Tyr was the most effective inhibitor of the fibroin-rabbit antifibroin precipitin reaction among the peptides tested that ranged in size from tetra- to octapeptides (40% inhibition at 5–18 μm/ml). The tetrapeptides were considerably less effective than Gly(Gly3,Ala3)Tyr although one of them, Gly(Gly,Ala)Tyr (20% inhibition at 18–20 μm/ml) has the same qualitative amino acid composition as the most effective octapeptide inhibitor. The dodecapeptide fraction was the most active of the peptides compared, giving 50% inhibition at 5–8 μm/ml. Removal of carboxyl-terminal tyrosine from the active octapeptides resulted in a halving of their effectiveness as inhibitors. The results indicate that, although tyrosine appears to account for a disproportionate part of the binding of peptide to antibody, a sizable segment (at least 8 to 12 residues) of the glycyl, alanyl chain is involved in specific combination.
Tập 86 Số 2 - Trang 205-214 - 1961
The Nature of an Antigenic Determinant Abstract
Immunochemistry has sought for many years to understand the exact chemical nature of an antigenic determinant and to know how it reacts with the extraordinarily complex and heterogeneous population of immunoglobulin molecules that possess regions complementary to it, e.g., antibody combining sites.
Tập 97 Số 1 - Trang 1-11 - 1966
Multiple Discrete Components of the Univalent Fragments of Rabbit Antibodies Summary
Specifically purified antibodies were prepared from the serum of individual rabbits or pooled sera from several rabbits hyperimmunized with bovine serum albumin (BSA) or ovalbumin. These were digested with papain and fractionated by column chromatography into the three major Porter fractions (I, II, III).
When subjected to disk electrophoresis, Fractions I and II each showed at least four components and Fraction III, three major components. Anti-BSA antibodies obtained from single rabbits gave essentially the same results as antibody prepared from pooled antiserum.
The intact specifically purified antibodies were shown to separate into two components by moving boundary electrophoresis. Sedimentation analysis, immunoelectrophoresis, and radioimmunoelectrophoresis showed the antibody preparations used were of the (160,000 MW) γ-globulin class. Immunoelectrophoresis of Fraction I and Fraction II showed a continuous distribution in electrophoretic mobility but did not separate into discrete bands.
The results suggest the presence of a limited number of discrete families of antibody molecules.
Tập 93 Số 1 - Trang 106-113 - 1964
The Heterogeneity of Combining Sites of Antibodies as Determined by Specific Immunoadsorbents Summary
Anti-Xp antibodies were fractionated by adsorption on immunoadsorbents and elution with haptens.
Different types of immunoadsorbent and various programs of elution with either different concentrations of a particular hapten or different haptens were used. In several cases, the eluted antibody was evaluated further with respect to heterogeneity by re-fractionation.
Some anti-Xp antibodies adsorbed on Xp-RSA-PAS could be eluted by o-substituted benzoate (0.3 M). Others not eluted by the first procedure were eluted by m-substituted benzoate and still others were eluted only by p-substituted benzoate. The observed order of effectiveness of substituents on elution was p-NO2 > p-Cl, m-NO2 > m-Cl > o-NO2 = o-Cl. There were some antibodies that were eluted by m-nitrobenzoate but not by p-chlorobenzoate and other that were eluted by p-chlorobenzoate but not by m-nitrobenzoate.
Very clear evidence was obtained that some of the antibodies could well accommodate an o-substituent on the hapten whereas other antibodies could not.
Each program of elution produced fractions with different properties. This indicated the heterogeneity of the original group of antibodies. However, each one of these fractions, when subjected to refractionation with a second program of elution, reflected the heterogeneity of the original population of antibody molecules going through this same second program.
The elution patterns were also characteristic of the immunoadsorbent. Almost all of the antibodies could be adsorbed on Xp-RSA-PAS, o-ClXp-RSA-PAS and m-NO2Xp-RSA-PAS but were eluted more easily by p-nitrobenzoate from the immunoadsorbents in the order, o-ClXp-, m-NO2Xp and Xp-RSA-PAS. X′-RSA-PAS and Xp-R-PAS failed to adsorb all antibodies and a part of the antibodies which were adsorbed was eluted more easily from these immunoadsorbents than from Xp-RSA-PAS.
The results provide evidence that some antibodies are directed not only to the haptenic group but also to the protein portion surrounding the haptenic group.
The amount of antibody was determined by labeling it with I131 or I125 and measuring the radioactivity. Effort and time could be saved and very close comparisons could be made by using the paired label technique in which one antibody fraction was labeled with I131 and the other labeled with I125 and the two passed simultaneously through the same column.
Tập 95 Số 3 - Trang 455-465 - 1965
The Heterogeneity of Combining Sites of Antibodies as Determined by Specific Immunoadsorbents Summary
The antigen-combining sites of rabbit anti-p-azobenzoate antibody were shown to be heterogenous by adsorption of antibody on a specific immunoadsorbent and by elution of the adsorbed antibody with haptens. A microanalytical method was developed for testing such heterogeneity with a few milligrams of antiserum globulin. The analyses could be performed rapidly and gave a very reproducible elution pattern. The method depended on the use of radioiodine labels. Two antibody preparations can be compared under precisely identical conditions by labeling one with I131, the other with I125 and passing the mixture through the fractionation procedures.
Tập 95 Số 3 - Trang 446-454 - 1965
Heterogeneity of Antibody Sites in Their Relative Combining Affinities for Structurally Related Haptens Summary
The heterogeneity of combining sites in an antihapten antibody was investigated by competitive binding, which provides a method for determining whether different sites tend to combine more strongly with different, closely related haptens; i.e., whether the ratio of K's for these haptens varies among the combining sites. Specifically, the effectiveness of varying concentrations of several haptens in displacing a reference hapten, radioactive p-iodobenzoate, from specifically purified anti-p-azobenzoate antibody was determined. Each hapten tested became relatively less effective as the degree of displacement increased, indicating heterogeneity of combining sites in their relative combining affinities for closely related substances. A correlation was noted between structural similarity of the competing hapten to the reference hapten and the magnitude of variation of the apparent relative K.
The results showed that each of the competing haptens was capable of displacing all or nearly all of the reference hapten if a sufficiently high concentration of competitor was used. Thus, there are few sites capable of combining with p-iodobenzoate which cannot also accommodate the other isomeric iodobenzoates.
In view of possible advantages of competitive binding as a means of estimating average equilibrium constants, the validity of the method was checked by comparison with direct binding, using 2 strongly bound haptens for the comparison, and with hapten inhibition of the precipitin reaction. Good agreement with the former method was observed. The agreement with hapten inhibition was only fair; differences were attributable to the nature of the reference substances displaced from antibody in the 2 methods (p-iodobenzoate vs. antigen).
Tập 81 Số 2 - Trang 126-135 - 1958
Cutting Edge: HMG-1 as a Mediator of Acute Lung Inflammation Abstract
Acute inflammatory lung injury is often a delayed complication of critical illness and is associated with increased mortality. High mobility group-1 (HMG-1) protein, in addition to its role as a transcriptional regulatory factor, has recently been identified as a late mediator of endotoxin lethality. In the present studies, HMG-1 given intratracheally produced acute inflammatory injury to the lungs, with neutrophil accumulation, the development of lung edema, and increased pulmonary production of IL-1β, TNF-α, and macrophage-inflammatory protein-2. In endotoxin-induced acute lung inflammation, administration of anti-HMG-1 Abs either before or after endotoxin exposure decreased the migration of neutrophils to the lungs as well as lung edema. These protective effects of anti-HMG-1 were specific, because pulmonary levels of IL-1β, TNF-α, or macrophage-inflammatory protein-2 were not decreased after therapy with anti-HMG-1. Together, these findings indicate that HMG-1 is a distal mediator of acute inflammatory lung injury.
Tập 165 Số 6 - Trang 2950-2954 - 2000