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Biomedical subjects

I Gigli

Publications and source records attributed to I Gigli.

At least 73 records · Page 4Linked to original sources
PubMed1984

Effect of combined topical glucocorticoids and ultraviolet B irradiation on epidermal Langerhans cells.

The combined effect of topical glucocorticoids and ultraviolet B (UVB) irradiation on ATPase+ epidermal Langerhans cells in vivo was investigated in the guinea pig model. Glucocorticoids did not significantly enhance the response to UVB radiation, in the dosage range from 90-550 mJ/cm2 of UVB, suggesting that both agents were acting in a similar fashion. The solvent ethanol, however, potentiated the effect of UVB exposure due, at least in part, to increased penetration of the UVB into the epidermis. The recovery of ATPase+ Langerhans cells was significantly slower after high (greater than 165 mJ/cm2) than after more moderate doses (90-145 mJ/cm2) of UVB radiation.

Adenosine Triphosphatases↗
PubMed1984

Activation of the complement system in patients with porphyrias after irradiation in vivo.

Irradiation of the forearms of two patients with erythropoietic protoporphyria and one patient with porphyria cutanea tarda resulted in an in vivo activation of the complement system, as assessed by diminution of the hemolytic titers of the third component of complement by 23-57%, and of the fifth component of complement (C5) by 19-47%. Such treatment also generated chemotactic activity for human polymorphonuclear cells; the chemotactic activity was stable at 56 degrees C and antigenically related to human C5. On Sephadex G-75 chromatography the chemotactic activity eluted with an apparent molecular weight of 15,000. These in vivo results extend our previous in vitro observation of photoactivation of complement in sera from patients with erythropoietic protoporphyria and porphyria cutanea tarda, and suggest that the complement system may participate in the pathogenesis of cutaneous phototoxicity in these patients.

Chemotaxis, Leukocyte↗
PubMed1983

Staining of Langerhans cells with monoclonal antibodies to macrophages and lymphoid cells.

Langerhans cells are Ia-bearing antigen-presenting cells in the epidermis that share many functions with macrophages. We have used monoclonal antibodies to the macrophage antigens, Mac-2 and-3, Ia antigen, Fc fragment receptor and the common leukocyte antigen CLA to compare the cell surface antigens of these cells with those of interdigitating and follicular dendritic cells and of macrophages in lymphoid tissues. Immunoperoxidase staining was carried out with epidermal sheets from BALB/c mice and epidermal cell suspensions enriched for Langerhans cells by Fc rosetting. Langerhans cells stained for all of these antigens. Comparison with the staining properties of other dendritic cells and macrophages, in combination with previous observations, indicates a close relationship of Langerhans cells to the interdigitating cells of lymphoid tissues.

Animals↗
PubMed1983

Effect of indomethacin on alteration of ATPase-positive Langerhans cell density and cutaneous sunburn reaction induced by ultraviolet-B radiation.

We have investigated the effect of ultraviolet-B (UVB) irradiation on the density of epidermal ATPase-positive Langerhans cells, and the modulation of this effect by indomethacin (IND). Depilated backs of albino guinea pigs were exposed to varying doses of UVB (10-550 mJ/cm2). Skin biopsies were taken serially. There was an UVB dose-dependent decrease in the density of dendritic epidermal Langerhans cells, as identified by their membrane ATPase activity. This was accompanied by thinning and shortening, or disappearance of dendritic processes. Such changes were followed by a gradual recovery of the cell density to preirradiation level by day 21. Despite the high doses of UVB given, the maximal decrease in the density of ATPase-positive cells was only 58%. Topical application of IND, a prostaglandin-synthetase inhibitor, after irradiation resulted in a decrease of the erythema; however, the decrease in the density of ATPase-positive cells was still observed. In contrast, guinea pigs that received IND topically prior to irradiation showed a decrease erythemal response, but failed to show any decrease in the density of ATPase-positive cells. Administration of IND orally for 3 days prior to UVB exposure did not prevent the decrease in the cell density. The protective effect of topical IND, applied prior to irradiation, may be explained by its in vitro absorbance at both the UVB and UVA ranges. Topical application of IND 20 min prior to exposure to UVB in 2 human subjects resulted in an increase in the minimal erythema dose, giving a sun protection factor of 1.6, which is comparable to that produced by an equimolar concentration of para-aminobenzoic acid solution. The sun-protective property of IND, together with its activity as a prostaglandin synthetase inhibitor, indicate that it potentially could be a useful sunscreen agent. Its clinical safety and efficacy, however, remain to be determined.

4-Aminobenzoic Acid↗
PubMed1983

Role of complement and polymorphonuclear cells in demethylchlortetracycline-induced phototoxicity in guinea pigs. Inhibition by decomplementation in vivo.

In this study, demethylchlortetracycline was used as a prototype of exogenous phototoxic substances. In vitro, exposure of serum containing demethylchlortetracycline to ultraviolet-A irradiation resulted in the diminution of total complement hemolytic activity and C4, C2, C3, and C5 activities. In addition, chemotactic activity for human polymorphonuclear cells was generated, which was thermostable and antigenically related to human C5 but not human C3. In vivo, phototoxic lesions were induced in guinea pigs upon intradermal injections of demethylchlortetracycline solution, followed by ultraviolet-A irradiation. On a scale of 0-3+, the animals developed a maximal response of 2.5 at 20 h. This clinical response was associated with cellular infiltrate in the dermis, consisting of 29 +/- 2% of neutrophils at 24 h. The participation of the polymorphonuclear cells was evaluated in guinea pigs rendered neutropenic by treatment with cyclophosphamide. In these guinea pigs, demethylchlortetracycline and ultraviolet-A induced a maximal response of 0.75 +/- 0.5, which was associated histologically with 1.2 +/- 0.5% neutrophils in the dermis. The role of complement in this process was studied in guinea pigs congenitally deficient in C4, and in guinea pigs decomplemented by treatment with cobra venom factor. In contrast to normal guinea pigs, C4-deficient animals exhibited a maximal reaction of 0.83 +/- 0.16 at 6 h, which subsided within 24 h. Cobra venom factor-treated guinea pigs developed a maximal response of 0.5 at 0.5 and at 6 h. These clinical changes were associated with the development of an increased vascular permeability, as demonstrated by studies using guinea pigs injected intravenously with Evans blue solution. In animals with a normal complement system, there was intense localized bluing at the sites of phototoxic lesion. In contrast, only minimal bluing was observed in decomplemented guinea pigs. These data indicate that a normal number of polymorphonuclear cells and an intact complement system are required for the full development of demethylchlortetracycline-induced phototoxic lesions.

Animals↗
PubMed1983

Requirements for the binding of human plasma fibronectin to the C1q subunit of the first component of complement.

We have shown previously that [125I]fibronectin (Fn) binds to solid-phase C1q in a dose-dependent manner. When C1r and C1s were added, the binding of Fn to C1q was abolished; removal of C1r and C1s restored Fn binding to C1q. In this report, we have systematically examined the optimal conditions that favor the Fn-C1q interaction. Our studies show that purified native 125I-Fn binds to C1q in a specific, saturable manner. Maximal 125I-Fn binding to C1q and gelatin occurs at low ionic strength (mu = 0.05) and drops sharply as the ionic strength is increased. At mu = 0.20, the binding to C1q is inhibited by 95%, whereas the binding to gelatin is inhibited by 50%. Optimal binding of Fn to C1q and gelatin occurs between pH 5.5 and 7.5, is decreased by 45% at 4 degrees C, and increases with incubation time; saturation of binding occurs in 60 min at 37 degrees C. Scatchard analysis of binding at mu = 0.05 indicates a single class of high affinity binding sites (Kd = 3.7 X 10(-8) M +/- 0.36 SD). The Kd of the reaction when C1q is bound to either plastic or immune complexes is essentially the same, and, in both cases, increases as the ionic strength of the medium is increased. Finally, significant binding of Fn to C1q can be demonstrated at physiologic ionic strength employing either insoluble immune complexes containing C1q or chemically cross-linked C1q.

Animals↗
PubMed1982

Activation of the guinea pig alternative complement pathway by mouse IgA immune complexes.

Activation of the complement system by IgA was investigated with immune complexes containing a mouse IgA myeloma protein with specificity for phosphorylcholine linked to bovine serum albumin (PC-BSA). These IgA anti-PC-BSA immune complexes activated the alternative complement pathway in mouse and guinea pig serum, while human complement was not affected. The activation proceeded with consumption of C3 but little or no consumption of C5. C3 did not bind to the IgA immune complexes during complement activation although it did bind covalently to IgG immune complexes. It is suggested that IgA immune complexes do not supply a suitable surface for C3 binding and effective alternative pathway convertase assembly; therefore, cleavage is limited and occurs primarily in the fluid phase. Without C3 binding, C5 cleavage does not occur nor can the alternative pathway activation proceed to the amplification step.

Animals↗
PubMed1982

Effect of glucocorticosteroids on epidermal Langerhans cells.

The effects of topical and systemic administration of various glucocorticoids on the density of epidermal Langerhans cells (LC) were studied in guinea pigs. Glucocorticoids, such as betamethasone dipropionate and valerate, caused a marked decrease in LC demonstrable by staining for cell membrane ATPase activity and Ia antigens. By electronmicroscopy, LC also showed morphologic alterations. The observed decrements in LC density correlated with the concentration and known vasoconstrictive potency of the glucocorticoids administered. The anti-inflammatory action of glucocorticoids in skin disorders may, at least in part, be through their ability to alter epidermal LC, thus interfering with the antigen-presenting functions of these cells.

Adenosine Triphosphatases↗
PubMed1982

Chido and Rogers antigenic determinant on the fourth component of human complement.

The blood group substances Chido (Cha) and Rogers (Rga) represent two electrophoretic variants of human C4. Based on the observation that anti-Cha and anti-Rga antisera agglutinated human red blood cells prepared in sucrose-activated autologous serum (LIS cells) at 37 degrees C, it has been assumed that the Cha and Rga antigenic determinants reside in the C4d fragment of C4. Here, we present evidence indicating that C4d is not present on those cells. In order to identify structurally the C4 fragments deposited, LIS cells were prepared at 37 degrees C and 4 degrees C in autologous serum to which 125I-C4 was added. Membranes of LIS cells were solubilized and analyzed by SDS-PAGE in 5 to 15% gradient gels followed by autoradiography. C4d was not deposited on LIS cells prepared at 37 degrees C, whereas C4c (beta, gamma, alpha 3 alpha 4) was. Cells prepared at 4 degrees C carried C4d (alpha 2) and C4c. Anti-Cha and anti-Rga antisera agglutinated both cell types, although C4d was not present on the cells prepared at 37 degrees C. Purified C4, C4c, C4d, and alpha-, beta- and gamma-chains of C4, as well as alpha 3 and alpha 4, were used to neutralize these antisera. C4 and the alpha-chain C4d and alpha 4 fragment of C4c, but neither the alpha 3 fragment nor the beta- or gamma-chains, were capable of neutralizing anti-Cha and anti-Rga antisera. These results strongly suggest that C4d and alpha 4 share an antigenic determinant, both of which are recognized by anti-Cha and anti-Rga antisera.

Blood Group Antigens↗
PubMed1982

The interaction of human plasma fibronectin with a subunit of the first component of complement, C1q.

Fibronectin is a normal plasma protein that enhances reticuloendothelial system functioning, and may participate in immune complex clearance. The interaction of 125I-fibronectin with human C1 and C1q in vitro was investigated by employing a highly reproducible solid-phase binding assay in microtiter wells. We demonstrated that although fibronectin does not bind to antigen-antibody complex (BSA-anti-BSA) or immune complexes containing C1, a 20-fold increase in binding was obtained when the complexes contained C1q alone. In the absence of antigen-antibody complexes, fibronectin binds to the C1q fixed to the wells in a dose-response fashion but not to intact C1. C1q in the fluid phase inhibits 85% of the fibronectin binding to immobilized C1q. The amount of fibronectin bound by immobilized C1q or gelatin is approximately equal. The binding of fibronectin to C1q could be inhibited by the restoration of C1r + C1s to the C1 macromolecular complex before the addition of fibronectin. The inhibition was dependent on the concentration of C1r + C1s and achieved a maximum of 70% at 100 micrograms/ml. This inhibition could be reversed by the removal of C1r and C1s subunits with EDTA or C1 inhibitor. Digestion of C1q with pepsin resulted in an 85% loss of fibronectin binding. It therefore appears that at least one site of fibronectin binding to C1q is in the globular portion of this complement component.

Animals↗
PubMed1982

The fourth component of human complement treated with amines or chaotropes or frozen-thawed (C4b-like C4): interaction with C4 binding protein and cleavage by C3b/C4b inactivator.

We have shown previously that C4 treated with amines or chaotropes, although uncleaved, exhibits properties that are similar to C4b. Studies by other groups suggest that this C4b-like form of C4 is characterized by the lack of an internal thiolester bond that is present in native C4. We report here that C4 treated with N2H4 or KSCN or frozen-thawed, unlike native C4, forms a complex with C4-binding protein (C4-bp) and is cleaved by C3b/C4b inactivator (I). Fragmentation of C4b-like C4 by I occurs without previous cleavage to C4b and requires the presence of C4-bp. Cleavage of C4b-like C4 proceeds in two steps: a small fragment (16,000 m.w.) is released first, followed by cleavage of the remaining alpha-chain fragment (83,000 m.w.) into polypeptides of 46,000 (C4d) and 32,000 m.w. All fragments, except the 46,000 m.w. fragment, are disulfide-linked to the beta- and/or gamma-chains of C4. Cleavage of C4b-like C4 probably occurs at the same points in the alp a-chain as in C4b; however, C4b-like c4 also contains C4a. Based on the m.w. determinations, the C4a portion of the alpha-chain is present in the 83,000 m.w. fragment, and after the second cleavage, in the 32,000 m.w. fragment of C4b-like C4. These findings suggest the following alignment of alpha-chain fragments: the N-terminal C4a portion is attached to a polypeptide of about 25,000 m.w. (alpha 3), which is followed in the sequence by C4d (alpha 2) (46,000 m.w.) and a small 16,000 m.w. fragment (alpha 4) that forms the C-terminus.

Amines↗
PubMed1982

Conformational changes in complement component C4 induced by activation, treatment with amines, chaotropes, or freezing-thawing, detectable by radioiodination using lactoperoxidase.

Conversion of C4 to C4b by enzymic cleavage or generation of a C4b-like form by treatment with amines, chaotropes, or freezing and thawing is accompanied by conformational alterations in the molecule. The nature of the changes is the same whether C4 is converted to a C4b-like form or to C4b. Evidence for structural changes at the surface of the C4 molecule was obtained by peripheral labeling with 125I by the lactoperoxidase method: there are residues, probably tyrosines, that are inaccessible for radioiodination in C4b and C4b-like C4, but exposed in native C4. The residues concerned are located in two separated parts of the alpha-chain at a distance of approximately 9000-34,000 m.w. from the N-terminus and in a 16,000 m.w. portion at the C-terminus. It is so far unknown whether the observed changes are involved in the uncovering of new binding sites, or whether they are the mere reflection of alterations elsewhere in the molecule that are of greater functional significance.

Amines↗
PubMed1981

Mechanism of action of the C4 nephritic factor. Deregulation of the classical pathway of C3 convertase.

Three mechanisms that regulate the formation and function of the classical pathway C3 convertase (C4b2a) have been elucidated: (a) an intrinsic decay of the enzyme that is temperature dependent; (b) an extrinsic decay mediated by the effect of the serum protein C4b binding protein (C4-bp); and (c) inactivation of C4b by the proteolytic action of C4b/C3b inactivator (C4b/C3bINA), which cleaves that alpha' chain of C4b to yield C4d (alpha 2) and C4c (alpha 3, alpha 4, beta, and gamma chains). A fourth mechanism described here is based on the observation that the IgG fraction of the serum of certain patients with glomerulonephritis contains a protein termed C4 nephritic factor (NFc), which prevents the intrinsic decay of C4b2a. This protein, which prolongs the half-life of surface-bound C4b2a from 7.5 min to greater than 5 h, increases the use of C3 and C5. It also inhibits the decay produced by C4-bp by preventing the dissociation of C2a from the C4b2a complex. Additionally, the C2b/C3bINA alone, or in the presence of C4-bp, fails to cleave the alpha' chain of C4b in the surface-bound stabilized C4b2a complex. This protective property of NFc requires the presence of C2a, because C4b was not protected unless it was bound to C2a. Thus in the presence of NFc, the three natural controls of the function of the classical pathway convertase, intrinsic decay, extrinsic decay, and proteolytic cleavage, are bypassed.

Animals↗