PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 3918838

Aspirin-sensitive asthma.

I K Slepian·K P Mathews·J A McLean
View original source ↗Export metadata ↓

Abstract

Aspirin intolerance is particularly common in asthmatic patients who additionally have chronic rhinitis and/or nasal polyps. These individuals differ in several respects from patients who experience urticaria and/or angioedema after aspirin administration, and differing mechanisms may be involved. Data regarding the latter are indirect and incomplete, but suggest that ASA-sensitive asthma is most likely to be related in some manner to the capacity of ASA to inhibit cyclooxygenases, enhanced lipoxygenase metabolism perhaps playing a crucial role. Current research employing ASA "desensitization" may help to elucidate these enigmas.

Explore related subjects

Arachidonic AcidArachidonic AcidsAspirinAsthmaDesensitization, ImmunologicDrug HypersensitivityHumansProstaglandin AntagonistsJournal ArticleResearch Support, U.S. Gov't, P.H.S.Review

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

I K Slepian, K P Mathews, J A McLean. 1985. Aspirin-sensitive asthma.. https://doi.org/10.1378/chest.87.3.386

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Expression of secretory phospholipase A2 in colon tumor cells potentiates tumor growth.

Secretory phospholipase A2 (sPLA2-IIA) has been shown to attenuate intestinal tumorigenesis in Apc(Min) mice, demonstrating that it is a tumor modifier. To further explore the actions of sPLA2-IIA in tumorigenesis, sPLA2-IIA was overexpressed in two cell lines where it is normally absent, the murine colon tumor cell line AJ02nm0, and human colon carcinoma cell line HCT-116. Two allelic variants of sPLA2-IIA were tested in this study; sPLA2-IIA(AKR) and sPLA2-IIA(SWR), which are derived from AKR/J and SWR/J mice, respectively, and differ by a single amino acid at position 63 in the calcium- and receptor-binding domain. There was no change in cell-doubling time for either allele when compared to vector controls. Furthermore, sodium butyrate and arachidonic acid (AA)-induced cell death were unchanged in control and transfected cells. Addition of the sPLA2 substrate, palmitoyl-arachidonoyl-phosphatidic acid (PAPA), to AJ02nm0 cells resulted in a modest (12%-24%), but significant (P < 0.01), inhibition of growth that was dependent on sPLA2-IIA expression. However, when AJ02nm0 and HCT-116 cells were injected subcutaneously (sc) into nude mice, Pla2g2a expression resulted in a 2.5-fold increase in tumor size. In addition, sPLA2-IIA expressing HCT-116 tumors were found to be more infiltrative than controls. We conclude that the ability of sPLA2-IIA to slow tumor cell growth is dependent upon the availability of substrate, and that in some instances sPLA2-IIA may actually enhance tumor growth. Mechanisms that may account for differences between the tumor explant model versus the Apc(Min) model of intestinal cancer are discussed.

Arachidonic Acid↗
PubMed2007

The role of arachidonic acid and its metabolites in insulin secretion from human islets of langerhans.

The roles played by arachidonic acid and its cyclooxygenase (COX)-generated and lipoxygenase (LOX)-generated metabolites have been studied using rodent islets and insulin-secreting cell lines, but very little is known about COX and LOX isoform expression and the effects of modulation of arachidonic acid generation and metabolism in human islets. We have used RT-PCR to identify mRNAs for cytosolic phospholipase A(2) (cPLA(2)), COX-1, COX-2, 5-LOX, and 12-LOX in isolated human islets. COX-3 and 15-LOX were not expressed by human islets. Perifusion experiments with human islets indicated that PLA(2) inhibition inhibited glucose-stimulated insulin secretion, whereas inhibitors of COX-2 and 12-LOX enzymes enhanced basal insulin secretion and also secretory responses induced by 20 mmol/l glucose or by 50 mumol/l arachidonic acid. Inhibition of COX-1 with 100 mumol/l acetaminophen did not significantly affect glucose-stimulated insulin secretion. These data indicate that the stimulation of insulin secretion from human islets in response to arachidonic acid does not require its metabolism through COX-2 and 5-/12-LOX pathways. The products of COX-2 and LOX activities have been implicated in cytokine-mediated damage of beta-cells, so selective inhibitors of these enzymes would be expected to have a dual protective role in diabetes: they would minimize beta-cell dysfunction while maintaining insulin secretion through enhancing endogenous arachidonic acid levels.

Arachidonic Acid↗