Kolasinski S L, Haines K A, Siegel E L, Cronstein B N, Abramson S B
Department of Medicine, New York University Medical Center, New York.
Arthritis Rheum. 1992 Apr;35(4):369-75. doi: 10.1002/art.1780350402.
Substance P and somatostatin are neuropeptides found in peripheral sensory nerves. In vitro, these have opposing effects on inflammatory cells. We compared the effects of these peptides on the activation of neutrophils.
Neutrophils were isolated from healthy volunteers, and chemotaxis, superoxide anion generation, aggregation, and changes in cytosolic calcium and GTPase activity were measured in the presence of substance P, somatostatin, and the chemoattractant FMLP.
Substance P was an effective chemoattractant, 20% as potent as FMLP at equimolar concentrations. Substance P also stimulated GTPase activity in neutrophil plasma membranes. Somatostatin did not activate neutrophils; however, it effectively inhibited neutrophil chemotaxis and GTPase activity provoked by substance P, but not by FMLP.
These studies demonstrate that substance P can effectively stimulate chemotaxis, possibly via effects on a GTP-binding protein distinct from that triggered by FMLP, and that somatostatin is a selective antagonist of substance P. The biochemical specificities of these peptides on cells may modulate neurogenic inflammation at the local level.
P物质和生长抑素是在周围感觉神经中发现的神经肽。在体外,它们对炎症细胞有相反的作用。我们比较了这些肽对中性粒细胞活化的影响。
从健康志愿者中分离出中性粒细胞,并在P物质、生长抑素和趋化因子FMLP存在的情况下测量趋化性、超氧阴离子生成、聚集以及细胞溶质钙和GTP酶活性的变化。
P物质是一种有效的趋化因子,在等摩尔浓度下其效力为FMLP的20%。P物质还刺激中性粒细胞膜中的GTP酶活性。生长抑素不激活中性粒细胞;然而,它有效地抑制了由P物质而非FMLP引起的中性粒细胞趋化性和GTP酶活性。
这些研究表明,P物质可能通过对一种不同于FMLP触发的GTP结合蛋白的作用来有效刺激趋化性,并且生长抑素是P物质的选择性拮抗剂。这些肽在细胞上的生化特异性可能在局部水平调节神经源性炎症。