Frevert C W, Huang S, Danaee H, Paulauskis J D, Kobzik L
Physiology Program, Harvard School of Public Health, Boston, MA 02115.
J Immunol. 1995 Jan 1;154(1):335-44.
Expression of mRNA for the neutrophil (PMN) chemokine, KC, in rat models of lung injury suggests a role for this chemokine in pulmonary inflammation. We addressed this hypothesis at the protein level by functionally characterizing recombinant rat KC (rKC) in vitro and in vivo. In vitro, rKC induced PMN chemotaxis and increased the expression of CD11b/CD18 on PMNs. Recombinant KC also induced a respiratory burst (quantitated by flow cytometry) in rat PMNs, similar to that caused by its human structural homologue, gro/melanoma growth-stimulating activity, on human PMNs, but less than that caused by IL-8 on human PMNs. Intratracheal instillation of rKC induced dose-dependent PMN influx into airspaces (average PMNs in bronchoalveolar lavage: vehicle = 1.5%, n = 4; rKC (1 microgram) = 11.5%, n = 2; rKC (10 micrograms) = 77.3%, n = 2). A neutralizing anti-KC Ab reduced the chemotactic activity of rat bronchoalveolar lavage fluid collected after the intratracheal administration of LPS (48.3 +/- 8% of control, n = 4). Anti-KC neutralizing Ab markedly inhibited PMN accumulation (71 +/- 6%) within the lungs in response to an intratracheal challenge of LPS. We conclude that rat KC is a major but not exclusive mediator of PMN activation and recruitment during LPS-induced pulmonary inflammation.
中性粒细胞（PMN）趋化因子KC的mRNA在大鼠肺损伤模型中的表达表明，该趋化因子在肺部炎症中发挥作用。我们通过在体外和体内对重组大鼠KC（rKC）进行功能特性分析，在蛋白质水平上验证了这一假设。在体外，rKC诱导PMN趋化，并增加PMN上CD11b/CD18的表达。重组KC还诱导大鼠PMN产生呼吸爆发（通过流式细胞术定量），类似于其人类结构同源物gro/黑素瘤生长刺激活性对人类PMN的作用，但低于IL-8对人类PMN的作用。气管内滴注rKC诱导剂量依赖性的PMN流入肺泡腔（支气管肺泡灌洗中的平均PMN：载体组=1.5%，n=4；rKC（1微克）=11.5%，n=2；rKC（10微克）=77.3%，n=2）。一种中和抗KC抗体降低了气管内注射LPS后收集的大鼠支气管肺泡灌洗液的趋化活性（为对照的48.3±8%，n=4）。抗KC中和抗体显著抑制了LPS气管内攻击后肺内PMN的积聚（71±6%）。我们得出结论，大鼠KC是LPS诱导的肺部炎症期间PMN激活和募集过程中的主要但非唯一介质。
