Cooper J A, Bridges T A, Kennedy J I, Culbreth R
Pulmonary Division, Birmingham Department of Veterans Affairs Medical Center 35233.
Am J Physiol. 1994 Jul;267(1 Pt 1):L71-8. doi: 10.1152/ajplung.1994.267.1.L71.
The lung is frequently exposed to particulate material that can potentially stimulate release of factors that attract polymorphonuclear neutrophils (PMN). However, few PMN are noted in the airways of normal subjects, suggesting there is some mechanism to dampen influx of these cells. We have isolated from bronchial lavage a peptide that inhibits PMN chemotaxis to formyl-methionyl-leucyl-phenylalanine (FMLP). In the present study we examined effects of this molecule on 1) chemotaxis to other agonists, 2) FMLP-stimulated PMN superoxide production, 3) PMN calcium fluxes, and 4) binding of FMLP. Our results show that purified inhibitor attenuates PMN chemotaxis to C5a and leukotriene B4. This molecule also inhibits PMN superoxide release in response to FMLP. Exposure to this inhibitor causes an abrupt rise in cytosolic calcium concentration due to a pertussis toxin-sensitive shift of intracellular calcium and attenuates subsequent influx of extracellular calcium in response to FMLP. Binding studies demonstrate the inhibitor induces increased FMLP binding at 37 degrees C but has no effects at 4 degrees C. Inhibition of chemotaxis and increased FMLP binding mediated by this molecule are attenuated by buffering PMN calcium transients. These studies suggest an inhibitor of neutrophil function present in the bronchial environment alters PMN through effects on calcium homeostasis.
肺经常暴露于可能刺激释放吸引多形核中性粒细胞（PMN）的因子的颗粒物质中。然而，在正常受试者的气道中很少发现PMN，这表明存在某种机制来抑制这些细胞的流入。我们从支气管灌洗中分离出一种抑制PMN对甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）趋化作用的肽。在本研究中，我们研究了该分子对以下方面的影响：1）对其他激动剂的趋化作用；2）FMLP刺激的PMN超氧化物生成；3）PMN钙通量；4）FMLP的结合。我们的结果表明，纯化的抑制剂可减弱PMN对C5a和白三烯B4的趋化作用。该分子还抑制PMN对FMLP的超氧化物释放。暴露于该抑制剂会导致胞质钙浓度突然升高，这是由于细胞内钙的百日咳毒素敏感移位，并且会减弱随后对FMLP的细胞外钙流入。结合研究表明，该抑制剂在37℃时诱导FMLP结合增加，但在4℃时无作用。通过缓冲PMN钙瞬变可减弱该分子介导的趋化作用抑制和FMLP结合增加。这些研究表明，支气管环境中存在的中性粒细胞功能抑制剂通过影响钙稳态来改变PMN。
