Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin cofactor II (HC) is a plasma serine proteinase inhibitor (serpin) that inhibits the coagulant proteinase alpha-thrombin. We have recently demonstrated that proteolysis of HC by catalytic amounts of polymorphonuclear leukocyte proteinases (elastase or cathepsin G) generates leukocyte chemotaxins (Hoffman, M., Pratt, C. W., Brown, R. L., and Church, F. C. (1989) Blood 73, 1682-1685). One of four peptides produced when HC is degraded by neutrophil elastase has chemotactic activity for both monocytes and neutrophils with maximal migration comparable to formyl-Met-Leu-Phe, the "gold standard" bacterially derived chemotaxin. The amino-terminal sequence of this HC peptide is Asp-Phe-His-Lys-Glu-Asn-Thr-Val-... and the peptide corresponds to Asp-39 to Ile-66 of HC. A variety of synthetic peptides derived from this sequence were evaluated for leukocyte migration activity, and a dodecapeptide from Asp-49 to Tyr-60 (Asp-Trp-Ile-Pro-Glu-Gly-Glu-Glu-Asp-Asp-Asp-Tyr) was identified as the active site for leukocyte chemotactic action. The 12-mer synthetic peptide possesses significant neutrophil chemotactic action at 1 nM (60% of the maximal activity of formyl-Met-Leu-Phe), while a peptide with the reverse sequence has essentially no chemotactic activity. Cross-desensitization experiments also show that pretreatment of neutrophils with a 19-mer peptide (Asn-48 to Ile-66) greatly reduces subsequent chemotaxis to HC-neutrophil elastase proteolysis reaction products. When injected intraperitoneally in mice, the HC-neutrophil elastase digest elicits neutrophil migration. Our results demonstrate that not only does HC function as a thrombin inhibitor, but that limited proteolysis of HC near the amino terminus yields biologically active peptide(s) which might participate in inflammation and in wound healing and tissue repair processes.
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PMID:Leukocyte chemoattractant peptides from the serpin heparin cofactor II. 198 58

This study investigated the reaction of heparin cofactor II (HCII) with stimulated polymorphonuclear leukocytes (PMN). We have expanded upon previous studies showing that HCII can be degraded by stimulated PMN (Sie, P., Dupouy, D., Dol, F., and Boneu, B., Thromb. Res. 47, 657-664, 1987), and that chemotactic activity is produced when HCII is partially proteolyzed with purified leukocyte elastase or cathepsin G (Hoffman, M., Pratt, C.W., Brown, R.L., and Church, F.C., Blood, 73, 1682-1695, 1989). We found that HCII was proteolyzed by stimulated PMN, generating peptides with chemotactic activity. Both proteolysis and generation of chemotactic activity were inhibited by a specific leukocyte elastase inhibitor and by more general proteinase inhibitors. Leukocyte elastase activity was lost upon addition of either inhibitor. Heparin and dermatan sulfate altered the pattern of proteolysis. Our results suggest that HCII may be involved not only in functions related to thrombin inhibition but also in regulating acute inflammation.
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PMID:Production of chemotactic peptides by neutrophil degradation of heparin cofactor II. 230 Sep 26

Antineutrophil cytoplasmic antibodies (ANCA) are present in sera from patients with various forms of vasculitis-associated glomerulonephritis. Because autoantibodies may be directed against antigens presented by apoptotic cells, generation of ANCA using apoptotic neutrophils (PMN) in syngenic Brown Norway (BN) rats was attempted. These rats are T-helper type 2-prone animals, already used successfully in other ANCA-positive animal models. BN rats received repeated injections of buffer or of nonapoptotic or apoptotic PMN aged in cultures, in the footpad and once intravenously. Four of five rats that received injections of PMN aged for 48 h developed ANCA, which cross-reacted with human leukocyte elastase in three cases. None of the rats that received injections of freshly isolated neutrophils developed ANCA. One rat that received buffer injection and that exhibited chronic skin infection developed delayed ANCA. None of the rats showed signs of disease: no weight loss and no proteinuria. Then a subnephritogenic dose of antibody directed against rat glomerular basement membrane was injected. Rats then were killed, and different organs were frozen and studied. No significant lesions were found in kidneys or lungs. It is concluded that injections of apoptotic but not freshly isolated PMN can generate ANCA in BN rats. Additional studies are needed to elucidate the immunization mechanism and the ability of these autoantibodies to initiate vasculitis in these experimental animals.
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PMID:Rats injected with syngenic rat apoptotic neutrophils develop antineutrophil cytoplasmic antibodies. 1146 51