Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin, well known anticoagulant, can also modulate inflammatory and immunologic processes. Some investigators suggest that heparin inhibits mast cell degranulation. Mast cells play very important role in early phase of asthmatic reaction, releasing many proinflammatory mediators including histamine. The purpose of study was to determine the effect of heparin on early asthmatic response and on histamine level in plasma after allergen challenge. Eleven patients with mild and moderate asthma were studied in a double blind placebo controlled manner. Sodium heparin or placebo were taken via nebulizer, and 15 minutes later allergen challenge (Dpt./grass pollen) was performed. FEV1 was measured at 5, 15, 30 and 60 minutes after challenge and PC20 for allergen was calculated. Peripheral blood was collected before and 30 minutes after challenge to assess histamine concentration in plasma by an immunoenzymatic assay. We observed that heparin significantly decreased early asthmatic response in all patients. After challenge with the same concentration of allergen FEV1 fell 36% for placebo and 8% for heparin. Heparin also prevented rise in histamine level in plasma after allergen challenge. The concentration of histamine before and after challenge were respectively 9.55 +/- 4.08 and 13.06 +/- 3.86 nM for placebo (p < 0.05) and 8.88 +/- 1.50 and 11.18 +/- 1.84 nM for heparin (p > 0.05). There was no correlation between FEV1 and histamine level before and after challenge. Our results suggest that heparin diminishes allergen induced early phase of asthmatic recreation by inhibition of mast cells degranulation.
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PMID:[The influence of heparin on histamine level in plasma during the early reaction phase of asthma]. 923 56

Accumulation of airway smooth muscle (ASM) and its infiltration by mast cells are key pathological features of airway remodelling in asthma. Heparin, a major component of mast cell granules, inhibits ASM proliferation by an unknown mechanism. Here, unfractionated heparins and related glycosaminoglycans having structurally heterogeneous polysaccharide side chains that varied in molecular weight, sulphation and anionic charge were used to identify features of the heparin molecule that were required for its antiproliferative activity in cultured human ASM cells. Proliferation induced by 10% fetal bovine serum (FBS) was abrogated by two unfractionated commercial heparin preparations (Sigma and Multiparin) and this effect was reproduced with each of three low-molecular weight heparin preparations (3, 5 and 6 kDa, respectively), demonstrating that antiproliferative activity resided in at least a 3 kDa heparin fraction. N-desulphated 20% re-acetylated (N-de) heparin (anticoagulant) and O-desulphated heparin (O-de) (non-anticoagulant) fractions also inhibited FBS-dependent proliferation (rank potency: Sigma heparin > O-de > N-de) suggesting that the antiproliferative action of heparin involved N-sulphation but was independent of its anticoagulant activity. Other sulphated molecules with variable anionic charge (dextran sulphate, fucoidan, chondroitin sulphates A or B, heparan sulphate) inhibited proliferation to varying degrees, as did the non-sulphated molecules hyaluronic acid and poly-L-glutamic acid. However, nonsulphated dextran had no effect. In summary, attenuation of FBS-dependent proliferation of human ASM by heparin involves but does not depend upon sulphation, although loss of N-sulphation reduces antiproliferative activity. This antiproliferative effect is independent of anionic charge and the anticoagulant actions of heparin.
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PMID:Some structural determinants of the antiproliferative effect of heparin-like molecules on human airway smooth muscle. 1602 36