Decreased H2 Histamine Response of Granulocytes of Asthmatic Patients

Busse, William W.; Sosman, Jeffrey A.

doi:10.1172/jci108731

Cited by 66 publications

(15 citation statements)

References 30 publications

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“…In recent years, reduced response to both fl-adrenergic and histamine H-2 receptor stimulation has been detected in leukocytes isolated from patients suffering from atopic diseases, such as asthma and atopic dermatitis [14][15][16][17]. In this study, the suppressive effect of D 4026 was investigated with cells from a fairly large number of blood donors, and it was shown that D4026 had the same capacity to inhibit the histamine release irrespective of whether the leukocytes were from normal donors or from patients suffering from atopic diseases (Fig.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of IgE-mediated histamine release from human leukocytes by a new xanthine derivative, D 4026

1980

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Pretreatment of human leukocytes with the new xanthine compound, 3,7-dihydro-1,8-dimethyl-3-phenyl-1H-purine-2,6-dione (D 4026), induced a dose-dependent and statistically significant inhibition of immunoglobulin E-mediated histamine release in the concentration interval 0.1-1000 microM. Histamine release elicited with suboptimum amounts of the triggering agent (anti-IgE or antigen) was inhibited to a greater extent than a release initiated with optimum amounts. At a concentration of 10 microM, D 4026 had at least the same inhibitory effect as 100 microM theophylline. When leukocytes were incubated simultaneously with D 4026 and a histamine H-2 receptor-stimulating drug (histamine or clonidine), the two drugs combined induced an inhibition significantly greater than the sum of their individual inhibitory effects. Only pure additive inhibitory effects were, however, obtained during simultaneous treatment of leukocytes with theophylline and histamine.

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Section: Discussionmentioning

confidence: 99%

Inhibition of IgE-mediated histamine release from human leukocytes by a new xanthine derivative, D 4026

1980

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“…Results of experiments recently ini tiated in our laboratory indicate a marked alteration of glomeruli cyclic nucleotides in PAN [22,23], In these experiments the ex tent of increases in glomerular cAMP levels elicited by histamine or serotonin was signif icantly lower in PAN. It is tempting to spec ulate that in response to histamine and sero tonin, lower intraglomerular cAMP forma tion may be associated with increased lysos omal enzyme release [24] and accelerated breakdown of glomerular glycoproteins. The results of our work are consistent with the concept that abnormal activities of lysos omal enzymes and increased lability of ly sosomes in glomeruli may be a pathogenic factor in the altered glycoprotein metabo lism in nephrotic syndrome.…”

Section: Discussionmentioning

confidence: 99%

Glomerular Lysosomal Enzymes in Aminonucleoside Nephrosis

Velosa¹,

Shah²,

Ou³

et al. 1980

Kidney Blood Press Res

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Lysosomal hydrolases produce degradation of glomerular basement membrane and may play a key role in catabolism of glycoproteins of extracellular matrix in glomeruli. Therefore we investigated activities of some lysosomal enzymes and stability of lysosomes in glomeruli of normal and nephrotic rats. Nephrosis was induced in rats by single injections of puromycin aminonucleoside. In glomeruli from nephrotic rats we found lower activities of β-fucosidase and arylsulfatase, but activity of acid phosphatase was higher compared with control rats. Osmotic stability of lysosomes measured by release of β-glucuronidase was decreased in nephrotic rats. Abnormal activity of lysosomal enzymes and altered physiology of lysosomes in glomeruli may be a pathogenic factor in the altered glycoprotein metabolism in nephrotic syndrome and perhaps also in other glomerular diseases.

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“…It seems likely that individual variations exist in H-1 or H-2 responsiveness as has been observed in mice (45). Indeed, asthmatic subjects appear to have impaired H-2 responses (46). Therefore, antigen-induced mediator release in the lungs of an asthmatic subject might initiate a series of responses including a relatively selective increase in cyclic GMP levels.…”

Section: Discussionmentioning

confidence: 99%