1999 Fiscal Year Final Research Report Summary
Studies on the molecular mechanism of neutrophil infiltration in inflammatory diseases
| Project/Area Number |
10672040
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Toyama Medical and Pharmaceutical University |
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Principal Investigator |
NAKAGAWA Hideo Toyama Medical and Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00012617)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Inflammation / Neutrophil infiltration / Allergic inflammation model / Chemokine / CINC / Air-pouch / LPS-induced inflammation model / Collagen typeXIV |
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| Research Abstract |
1. Purification of a novel neutrophil chemotactic factor from rat granulation tissue :
A novel neutrophil chemotactic factor has been purified from the granulation tissue of air-pouch/carrageenin-induced inflammation in rats. The purified chemoattractant was a basic protein with heparin-binding site, and gave a single band corresponding to a molecular mass of 16-kDa on SDS-PAGE under reducing conditions. The chemoattractant was treated with lysylendopeptidase and the resulting peptides were isolated by reversed-phase HPLC. Amino acid sequences of the peptides were almost identical with the sequence of N-terminal fibronectin type III domain of human collagen type XIV, suggesting that the purified chemoattractant consists mainly of N-terminal fibronectin type III domain and the adjacent heparin-binding site of rat collagen type XIV. The 16-kDa fragment of collagen type XIV dose-dependently attracted rat neutrophils and transiently increased the intracellular free CaィイD12+ィエD1 concentratio
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n of neutrophils. The results suggest that the novel chemoattractant play a role in neutrophil recruitment in rat inflammation.
2. Roles of chemokines in neutrophil infiltration in rat inflammation models :
In the present study, by use of ELISA specific for each chemokine, we have determined the levels of the chemokines (CINC-1, -2, -3 and rat MIP-1α) in the pouch fluids of two types of inflammation models (FITC-ovalbumin-induced allergic inflammation and LPS-induced inflammation in rats). Effects of anti-chemokine antibodies on neutrophil chemotaxis were determined in vivo and in vitro. Anti-CINCs-antibodies, which inhibited all the CINCs, suppressed both neutrophil infiltration in vivo and neutrophil chemotactic activity of the 8-hr pouch fluid in vitro, whereas anti-MIP-1α antibody slightly suppressed the chemotaxis in vivo and in vitro. Our results suggest that CINC-1/-2 for the allergic inflammation and CINC-2/-3 for the LPS-induced inflammation, respectively, play an important role in infiltration of neutrophils into inflammatory sites of rat inflammation models. Less
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Research Products
(4 results)
