OBJECTIVETo study the effects of very late antigen(VLA) antagonist BIO-1211 on eosinophil chemotaxis, recruitment and mediator release.

METHODSEosinophil chemotaxis was induced by platelet activating factor(PAF) in vitro and eosinophil recruitment and release were determined in vivo.

RESULTVLA antagonist BIO-1211 inhibited eosinophil chemotaxis induced by PAF. The inhibitory rates at 4x10(-11), 4x10(-10), 4x10(-9) mol x L(-1) were 24.9%, 29.9%, and 31.3%, respectively. Pretreatment by BIO-1211 1, 3 and 10 mg x kg(-1) intraperitoneally inhibited the recruitment of eosinophils in PAF in the rat induced by Sephadex in a dose dependent manner. Inhibitory rates were 60.3%, 68.9%, and 72.9%(P<0.05), respectively. BIO-1211 did not inhibit eosinophil peroxidase(EPO) release from eosinophils.

CONCLUSIONBIO-1211 inhibits eosinophil chemotaxis and recruitment, alleviates local inflammation, and may represent a new type of drug for allergic diseases.

Animals ; Cell Movement ; drug effects ; Chemotaxis, Leukocyte ; drug effects ; Dose-Response Relationship, Drug ; Eosinophil Peroxidase ; Eosinophils ; drug effects ; physiology ; Integrin alpha4beta1 ; antagonists & inhibitors ; physiology ; Male ; Oligopeptides ; pharmacology ; Peroxidases ; secretion ; Platelet Activating Factor ; pharmacology ; Rats ; Rats, Sprague-Dawley

In this study, we observed that lysophosphatidylglycerol (LPG) completely inhibited a formyl peptide receptor like-1 (FPRL1) agonist (MMK-1)-stimulated chemotactic migration in human phagocytes, such as neutrophils and monocytes. LPG also dramatically inhibited IL-1beta production by another FPRL1 agonist serum amyloid A (SAA) in human phagocytes. However, LPG itself induced intracellular calcium increase and superoxide anion production in human phagocytes. Keeping in mind that phagocytes migration and IL-1beta production by FPRL1 are important for the induction of inflammatory response, our data suggest that LPG can be regarded as a useful material for the modulation of inflammatory response induced by FPRL1 activation.
Chemotaxis, Leukocyte/*drug effects ; Humans ; Interleukin-1beta/*biosynthesis ; Lysophospholipids/*pharmacology ; Monocytes/drug effects/immunology/metabolism/physiology ; Neutrophils/drug effects/immunology/metabolism/physiology ; Peptides/metabolism/pharmacology ; *Phagocytes/drug effects/immunology/metabolism/physiology ; Receptors, Formyl Peptide/*metabolism ; Receptors, Lipoxin/*metabolism ; Serum Amyloid A Protein/metabolism/pharmacology

OBJECTIVETo investigate the effects of Musk glucoprotein on chemotaxis of Polymorphonuclear leukocytes(PMN).

METHODThe chemotaxis of PMN in abdominal cavity in rat induced by carboxymethyl cellulose(CMC) was used as an in vivo animal model and in in vitro it was evaluated by Boyden chamber. The concentration of cytosolic free Ca2+ was quantitated with the fluorescent Ca2+ indicator Fura-2.

RESULTThe water extract of Musk at dose of 5, 20, 80 mg.kg-1 (s.c.) significantly inhibited the chemotaxis of PMN in rat; Musk-1 at concentration of 1-100 micrograms.mL-1 can significantly inhibit the chemotaxis of rabbit PMN in vitro; Musk-1 at concentration of 1-100 micrograms.mL-1 can significantly inhibit the increase of cytosolic Ca2+ concentration in PMN of rat.

CONCLUSIONPart of mechanisms underlying antiinflammatory action of Musk is to inhibit the chemotaxis of PMN.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Calcium ; metabolism ; Chemotaxis, Leukocyte ; drug effects ; Fatty Acids, Monounsaturated ; chemistry ; pharmacology ; Female ; Glycoproteins ; isolation & purification ; pharmacology ; Male ; Materia Medica ; isolation & purification ; pharmacology ; Neutrophils ; metabolism ; physiology ; Rabbits ; Rats ; Rats, Wistar

AIMTo study the inhibitory effect of ginkgolide B (BN52021) on the PAF induced changes of chemotaxis of murine peritoneal macrophages and the related polymerization of F-actin.

METHODSChemotaxis assays were performed using a modified 48-well Boyden chamber. Actin polymerization of murine peritoneal macrophages was analyzed by flow cytometry using a specific fluorescent stain.

RESULTSPeritoneal macrophages significantly migrated toward platelet-activating factor (PAF) through a micropore filter; however, in the presence of PAF receptor antagonist BN52021 (0.01 nmol x L(-1) -0.1 micromol x L(-1)), the migration was significantly inhibited. Moreover, BN52021 inhibited the actin polymerization of murine peritoneal macrophages induced by PAF in the presence of Ca2+, but not in Ca2+ -free medium.

CONCLUSIONThe results suggested that preventing polymerization of F-actin may be a pathway by BN52021 to inhibit the chemotaxis of macrophages, and this effect seems to be Ca2+ dependent. The data further indicated that inhibition of PAF induced macrophage chemotaxis is an important mechanism underlying the anti-inflammatory action of BN52021.

Actins ; metabolism ; Animals ; Chemotaxis, Leukocyte ; drug effects ; Diterpenes ; isolation & purification ; pharmacology ; Ginkgo biloba ; chemistry ; Ginkgolides ; Lactones ; isolation & purification ; pharmacology ; Macrophages, Peritoneal ; metabolism ; physiology ; Mice ; Mice, Inbred C57BL ; Plants, Medicinal ; chemistry ; Platelet Activating Factor ; antagonists & inhibitors

Cells, Cultured ; Chemokine CCL4 ; Chemotaxis, Leukocyte ; drug effects ; Endothelial Cells ; cytology ; metabolism ; Homocysteine ; pharmacology ; Humans ; Macrophage Inflammatory Proteins ; biosynthesis ; genetics ; Monocytes ; physiology ; RNA, Messenger ; biosynthesis ; genetics ; Umbilical Veins ; cytology

His-Phe-Tyr-Leu-Pro-Met (HFYLPM) is a synthetic peptide that stimulates Jurkat T cells resulting in intracellular calcium ([Ca2+]i) increase in a pertussis toxin (PTX)-sensitive manner. We have examined the physiological role of the peptide in T cell activity by comparative investigation of intracellular signaling pathways accompanied with HFYLPM-induced T cell chemotaxis with a well-known chemokine, stromal cell-derived factor-1 (SDF-1)-induced signalings. Wortmannin and genistein inhibited both of HFYLPM- and SDF-1-induced Jurkat T cell chemotaxis indicating that phosphoinositide-3-kinase and tyrosine kinase activity were required for the processes. However, U-73122 and BAPTA/AM preferentially blocked HFYLPM- but not SDF-1-induced T cell chemotaxis. It indicates that phospholipase C/calcium signaling is necessary for only chemotaxis by HFYLPM. One of the well-known cellular molecules involving chemotaxis, extracellular signal-regulated protein kinase (ERK), was activated by SDF-1 but not by HFYLPM ruling out a possible role of ERK on the peptide-mediated chemotaxis. These results indicate that the synthetic peptide, HFYLPM, stimulates T cell chemotaxis showing unique signaling and provide a useful tool for the study of T cell activation mechanism.
1-Phosphatidylinositol 3-Kinase/metabolism ; Androstadienes/pharmacology ; Calcium/metabolism ; Cell Line ; Chemokines, CXC/*pharmacology ; Chemotaxis, Leukocyte/drug effects/*physiology ; Dose-Response Relationship, Drug ; Genistein/pharmacology ; Human ; Jurkat Cells ; Oligopeptides ; Peptide Fragments/chemical synthesis/metabolism/*physiology ; Pertussis Toxin ; Phospholipase C/metabolism ; Protein-Tyrosine Kinase/metabolism ; Signal Transduction/drug effects ; T-Lymphocytes/*drug effects ; Virulence Factors, Bordetella/pharmacology

His-Phe-Tyr-Leu-Pro-Met (HFYLPM) is a synthetic peptide that stimulates Jurkat T cells resulting in intracellular calcium ([Ca2+]i) increase in a pertussis toxin (PTX)-sensitive manner. We have examined the physiological role of the peptide in T cell activity by comparative investigation of intracellular signaling pathways accompanied with HFYLPM-induced T cell chemotaxis with a well-known chemokine, stromal cell-derived factor-1 (SDF-1)-induced signalings. Wortmannin and genistein inhibited both of HFYLPM- and SDF-1-induced Jurkat T cell chemotaxis indicating that phosphoinositide-3-kinase and tyrosine kinase activity were required for the processes. However, U-73122 and BAPTA/AM preferentially blocked HFYLPM- but not SDF-1-induced T cell chemotaxis. It indicates that phospholipase C/calcium signaling is necessary for only chemotaxis by HFYLPM. One of the well-known cellular molecules involving chemotaxis, extracellular signal-regulated protein kinase (ERK), was activated by SDF-1 but not by HFYLPM ruling out a possible role of ERK on the peptide-mediated chemotaxis. These results indicate that the synthetic peptide, HFYLPM, stimulates T cell chemotaxis showing unique signaling and provide a useful tool for the study of T cell activation mechanism.
1-Phosphatidylinositol 3-Kinase/metabolism ; Androstadienes/pharmacology ; Calcium/metabolism ; Cell Line ; Chemokines, CXC/*pharmacology ; Chemotaxis, Leukocyte/drug effects/*physiology ; Dose-Response Relationship, Drug ; Genistein/pharmacology ; Human ; Jurkat Cells ; Oligopeptides ; Peptide Fragments/chemical synthesis/metabolism/*physiology ; Pertussis Toxin ; Phospholipase C/metabolism ; Protein-Tyrosine Kinase/metabolism ; Signal Transduction/drug effects ; T-Lymphocytes/*drug effects ; Virulence Factors, Bordetella/pharmacology

AIMTo investigate the effect of ginkgolide B on PAF-induced adhesion, chemotaxis and degranulation of rat polymorphonuclear leukocytes (PMNs).

METHODSThe adhesion of rat PMNs to rat synovial cells (RSC) was measured with MTT colorimetry. The chemotaxis of PMNs was quantified with Boyden chamber method. The degranulation of rat PMNs was evaluated by determining the activity of released beta-glucuronidase.

RESULTSIn comparison with control, ginkgolide B at the concentration of 10 mumol.L-1 significantly inhibited the adhesion of PMNs to RSC by 71.74%. At the final concentration of 1-1,000 nmol.L-1, ginkgolide B dose-dependently inhibited the chemotaxis of PMNs stimulated with 10 nmol.L-1 platelet-activating factor (PAF), the IC50 was 4.84 nmol.L-1. At the final concentration of 0.01-10 mumol.L-1, ginkgolide B decreased the release of beta-glucuronidase in PMNs induced by 1 mumol.L-1 PAF in dose-dependent manner. The IC50 was 3.56 mumol.L-1.

CONCLUSIONGinkgolide B was found to significantly inhibit PAF-induced adhesion, chemotaxis and degranulation in rat polymorphonuclear leukocytes. These effects might be considered a part of the mechanisms underlying the antiinflammatory action of ginkgolide B.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Cell Adhesion ; drug effects ; Cells, Cultured ; Chemotaxis, Leukocyte ; drug effects ; Diterpenes ; isolation & purification ; pharmacology ; Drug Interactions ; Ginkgo biloba ; chemistry ; Ginkgolides ; Glucuronidase ; metabolism ; Lactones ; isolation & purification ; pharmacology ; Male ; Neutrophils ; drug effects ; physiology ; Plants, Medicinal ; chemistry ; Platelet Activating Factor ; antagonists & inhibitors ; pharmacology ; Rats ; Rats, Wistar