Paf-acether (platelet-activating factor) and interleukin-1-like cytokine production by lipopolysaccharide-stimulated glomeruli.

The production of inflammatory mediators by glomerular cells may be instrumental in the development of pathophysiological alterations during glomerulonephritis. Since bacterial lipopolysaccharide (LPS) is a naturally occurring immunological stimulus, we studied its inflammatory effects on isolated renal glomeruli. LPS stimulation of human and rat isolated glomeruli resulted in a dose- and time-dependent platelet-activating factor (paf-acether) production. Maximal paf-acether generation (1.04 to 1.50 ng/mg protein) (n = 18) was obtained when glomeruli were stimulated for periods of 1 to 4 hr and with 1-2 micrograms/ml LPS. Paf-acether derived from human and rat glomeruli exhibited identical biological and physicochemical characteristics. In addition, rat glomeruli stimulated with doses of LPS from 100 ng to 50 micrograms/ml released an Interleukin-1 (IL-1)-like cytokine differing in part from that described in cultured mesangial cells. Maximal release of IL-1-like activity by rat glomeruli was obtained after 24 to 48 hr incubation in the presence of LPS. After gel chromatography resolution, the glomerular cytokine presented IL-1-like activity in fractions corresponding to molecular weights of 15-35 and 4-8 kDa. The latter compounds could represent metabolites similar to those described in normal urine. Thus the local release of paf-acether and IL-1-like cytokine by glomeruli in response to bacterial stimuli may represent a prominent feature of glomerular inflammation.

Specificity of antibodies to heterologous glomerular and tubular basement membranes in various strains of mice with different H-2 types.

C3H, CBA (H-2k) and NZB (H-2d) mice were immunized with dog insoluble glomerular (GBM) or tubular basement membrane (TBM). The titre of circulating antibodies was sequentially determined and their specificity was analysed using various soluble antigenic fractions. Glomerular and tubular deposits were studied on serial biopsies by direct immunofluorescence. After elution from whole kidneys, IgG fixation on normal mouse kidney sections was analysed by indirect immunofluorescence. After immunization with insoluble GBM, animals from all three strains develop antibodies mainly directed against collagenous antigenic determinants shared by GBM and TBM. After immunization with insoluble TBM, the antibodies are directed in NZB mice against non-collagenous TBM-specific determinants, in C3H mice against collagenous determinants and in CBA mice against both types of antigenic determinants. Thus the ability to respond to the various antigens of GBM and TBM is genetically determined and does not depend only on the major histocompatibility complex.

Specificity of antibodies to heterologous glomerular and tubular basement membranes in BALB/c mice.

Balb/c mice were immunized with dog insoluble glomerular basement membrane (GBM) or tubular basement membrane (TBM). The titre of circulating antibodies was sequentially determined and their specificity was analysed using various soluble membrane fractions. Glomerular and tubular deposits were studied on serial biopsies by direct immunofluorescence. After elution, from whole kidneys, IgG fixation on normal mouse kidney sections was analysed by indirect immunofluorescence. The conclusions are the following: (a) after immunization with insoluble GBM, the antibodies are mainly directed against collagenous antigenic determinants shared by GBM and TBM; (b) after immunization with insoluble TBM, the antibodies are mainly directed against noncollagenous TBM-specific antigenic determinants.

Regulation of contact sensitivity to DNFB in the mouse: effects of adult thymectomy and thymic factor.

The contact sensitivity response to DNFB is decreased after adult thymectomy (ATX). This response decreases to 50% of the control response of normal age-matched mice as soon as 3 weeks after ATX and is not further depressed 9 to 16 weeks after ATX. These results suggest that two T cell subsets of different lifespan are involved in the anti-DNFB response. A circulating thymic factor (FTS) is able to restore the contact sensitivity response to DNFB when injected 3 to 9 weeks after ATX but not 16 weeks later. By contrast, FTS has a depressive effect on the contact sensitivity response to DNFB of normal mice through a cyclophosphamide-sensitive T cell subset. These results suggest that FTS regulates DNFB contact sensitivity by acting on a cyclophosphamide-sensitive T cell subset, still present 9 weeks after ATX but absent after 16 weeks. Thus although the T cell defect, causing a depression of the contact sensitivity reaction to DNFB is quantitatively similar 3 and 16 weeks after ATX, its nature is probably different.

[T-Lymphocyte regulation of contact sensitivity: effect of thymectomy in adult mice]. / Régulation de l'hypersensibilité de contact par les lymphocytes T : effet de la thymectomie à l'âge adulte chez la Souris.

6 weeks after adult thymectomy (ATx) in the Mouse, the contact sensitivity reaction to dinitrofluorobenzene (DNFB) is enhanced. 4 to 7 months after ATx, this reaction is deeply, but incompletely depressed, whereas the concomitant antibody response is not affected. These results suggest that both a suppressor, and an amplifier, T lymphocytes, the life span of which is different after ATx, are involved in the regulation of contact sensitivity. The effect of circulating thymic factor on this reaction suggests that this factor acts exclusively, at least in short treatments, on the suppressor function.

[Modification of the immune response by a hepatic ferroglobulin: L alpha2-HF]. / modifications des réponses immunitaires sous l'influence d'une ferroglobuline hépatique: L' alpha2-HF

Alpha2-HF, foetal and tumorous isoferritin, the level of which is high in cancerous patients and in amniotic fluid during pregnancy, has an immunosuppressif effect on normal lymphocytic response. Its activity has been tested on blastic transformation induced by PHA, tuberculin, candidin and allgenic lymphocytes. The inhibition effect is proportional to the added quantity of alpha2-HF globulin. The antibody synthesis is depressed by alpha2-HF as demonstrated in vivo and in vitro. Iron is no responsible for the suppressif effect: the efficiency is identical with the native protein or the apo-protein. Crystallised ferritin, without sugar in its molecule on the contrary of alpha2-HF which is a glycoferroprotein, has no suppressif effect.

[Immunosuppressive effect of a human serum ferroprotein of hepatic origin: alpha-2-HF-globulin]. / Effet immunosuppresseur d'une ferroprotéine sérique humaine d'origine hépatique l'alpha 2 HF-globuline. Action sur la synthèse des anticorps in vitro

alpha 2HF, a serum ferroprotein increased during some malignant diseases, displays a suppressive effect on in vitro antibody responses, whether T-independent or T-dependent. This effect is not related to the presence of iron, nor to the macroglobulin nature of the molecule. The immunosuppressive properties of alpha 2 HF might depend on its carbohydrate moeity.