IL-4 inhibits macrophage-mediated killing of Plasmodium falciparum in vitro. A possible parasite-immune evasion mechanism.

Although a number of mechanisms have been put forward for immunity to malaria, their importance remains to be clarified. One of the important findings is that nonactivated monocytes and macrophages showed marked antiplasmodial activity in vitro. Recently we postulated that parasites may induce host factors that may depress the natural antiplasmodial activity of monocytes. In this investigation we identify IL-4 as a lymphokine that could function in this capacity. Human monocytes and macrophages in the absence of antiplasmodial antibody showed substantial killing of the asexual erythrocytic forms of Plasmodium falciparum as determined by a radiometric assay. Suppression of this killing was seen if the mononuclear phagocytes were pretreated with human rIL-4 at concentrations of 10 to 250 U with optimum activity between 100 and 250 U/2 x 10(5) cells. Cells from some individuals were rendered completely inactive by the IL-4 treatment. In contrast, IL-4 did not affect the neutrophil-mediated anti-P. falciparum activity. Our work identifies a potentially important parasite immune evasion mechanism involving IL-4 suppression of macrophage antiparasite activity.     

Potentiation of the antagonistic effect of ACTH11-24 on steroidogenesis by synthesis of covalent dimeric conjugates

Covalent dimerization of the adrenocorticotropin fragment ACTH11-24 increases its antagonistic potency on the ACTH-induced steroidogenesis in isolated bovine fasciculata/reticularis cells by 3 orders of magnitude when the C-termini are linked via a 10 A long spacer. This strong potentiation, probably mediated by cross-linking of the receptors, was shown to be dependent on the point of attachment of the monomeric fragment to the spacer, thus providing information about the position of the binding site in the hormonal segment and about the distance of the receptors on the cell surface.     

Evidence for a non-steroidal angiotropic factor from the primate corpus luteum: stimulation of endothelial cell migration in vitro

After luteal cells from 7 midluteal phase cynomolgus monkeys were cultured for 72 h, luteal conditioned media were found to contain angiotropic activity that stimulated endothelial cell migration in vitro, using a 48-microwell chemotaxis assembly. The number of endothelial cells that migrated through 8 micron-pore polycarbonate membranes in 2 h was three-fold greater (P less than 0.01) with luteal cell-conditioned vs identical unconditioned media. Pre-treatment of luteal cultures with hCG, FSH, or testosterone did not enhance production of the endothelial cell migration stimulating activity (P greater than 0.25). Luteal angiotropic activity was both chemotactic and chemokinetic. Angiotropic activity was retained in steroid-depleted fractions after reversed-phase chromatography. These results demonstrate that monkey luteal cells secrete a non-steroidal factor(s) which directly stimulate(s) migration of endothelial cells in vitro. A luteal angiotropic factor may be an important intraovarian regulator of the formation and lifespan of the primate corpus luteum during the ovarian cycle.     

Effect of alkylresorcin on biological membranes during activation of lipid peroxidation

The effect of alkyl resorcin isolated from the cells of Azotobacter chroococcum and of its structural analog devoid of the alkyl chain (resorcin) on liver microsomes and brain synaptosomes of the rat as well as on rabbit skeletal muscle sarcoplasmic reticulum fragments during activation of lipid peroxidation was studied. Alkyl resorcin was shown to produce a much more potent antioxidant effect as compared with resorcin, since it inhibited lipid peroxidation in all the three types of membranes under study at much lower concentrations. Both alkyl resorcin and resorcin which inhibit lipid peroxidation prevented lipid peroxidation-induced structural-functional damages of synaptosomal and sarcoplasmic reticulum fragment membranes. Unlike resorcin, alkyl resorcin exerted an additional effect on brain synaptosomal membranes which consisted in the stabilization of barrier functions of membranes during incomplete inhibition of lipid peroxidation. The cumulative data suggest that stabilization necessitates the presence of both resorcin radical and alkyl chain in the alkyl resorcin molecule.     

Block by phencyclidine of acetylcholine and barium induced adrenal catecholamine secretion

Activation of the sympathetic system by phencyclidine (PCP) should result in catecholamine release from the adrenals. However, adrenalectomy does not reduce PCP-induced hypertension. In an attempt to rectify this inconsistency, the direct effects of PCP on the bovine adrenal medulla were examined. At (3×10^?6M), PCP reduced the acetylcholine-(ACh)-induced catecholamine release by 50%. Surprisingly, barium-induced secretion of catecholamines was also reduced by PCP. ACh-induced catecholamine release was not altered by 10^?3M 4-aminopyridine (4 AP), the potassium channel blocker. Thus, calcium antagonist actions of PCP and consequent block of catecholamine secretion from adrenal medulla may explain the lack of effect of adrenalectomy on PCP-induced hypertension. Possible contributions of calcium and/or potassium channel blockade to other manifestations of PCP overdosage are discussed.     

Developmental regulation of myelin basic protein expression in mouse brain

Developmental regulation of myelin basic protein expression in mouse brain has been examined by comparing the myelin basic protein coding potential of mRNA in vitro with the accumulation of myelin basic protein-related polypeptides in vivo. In vitro translation of mRNA isolated from mouse brain generated eight myelin basic protein-related polypeptides with apparent molecular weights of 34K, 30K, 29K, 26K, 21.5K, 18.5K, 17K, and 14K. A similar set of eight myelin basic protein-related polypeptides with corresponding molecular weights was identified in vivo when total brain proteins were analyzed by immunoblotting. Each of the myelin basic protein-related polypeptides shows a characteristic developmental profile in terms of mRNA level and rate of accumulation implying a complex developmental program of myelin basic protein gene expression with regulation and modulation at several different biosynthetic levels.     

Mercuric chloride-induced nephrotoxicity in the rat following unilateral nephrectomy and compensatory renal growth

The nephropathy induced by mercuric chloride was assessed in unilaterally nephrectomized (NPX) and sham-operated (SO) rats using histological and urinalysis techniques. This assessment was carried out in order to test whether or not rats are more susceptible to the nephrotoxic effects of mercuric chloride after unilateral nephrectomy and a period allowing for compensatory renal growth. Twelve days after surgery both NPX and SO rats were given a single 1.5, 2.0 or 2.5 mumol/kg dose of mercuric chloride (i.v.). Twenty-four hours after the 1.5 or 2.0 mumol/kg dose of mercuric chloride was administered, cellular and tubular necrosis in the pars recta segments of proximal tubules in the outer medulla was more severe in NPX rats than in SO rats. Moreover, the urinary excretion of a number of cellular enzymes (e.g. lactate dehydrogenase) and plasma solutes (e.g. albumin) was greater in NPX rats than in SO rats. At the 2.5 mumol/kg dose of mercuric chloride, renal tubular damage was quite extensive in both groups of rats; to such an extent that possible differences in renal tubular damage between the NPX and SO rats could not be determined histologically. However, the urinary excretion of alanine aminopeptidase was greater in the NPX rats than in the SO rats. Therefore, based on the aforementioned findings, rats that have undergone and adapted to a reduction in renal mass (i.e. unilateral nephrectomy) appear to be more vulnerable to the nephrotoxic effects of mercuric chloride than rats with two normal kidneys.