神经生长因子不同给药方式对坐骨神经吻合后修复与再生的影响

背景：神经生长因子对神经损伤后的修复有促进作用,但目前对不同用药方式的优劣性尚有争议。目的：观察鞘膜内与局部应用神经生长因子对兔坐骨神经吻合后修复与再生的影响。方法：将24只新西兰大白兔坐骨神经切断后再缝合,分别向兔鞘膜内或损伤局部注射30μg神经生长因子或等量生理盐水结果与结论：坐骨神经损伤后12周,鞘膜内注射神经生长因子组损伤坐骨神经鞘膜增厚,神经纤维排列较整齐,与正常神经纤维差异不大;且其神经干传导速度、有髓神经纤维数目、髓鞘厚度也明显高于其他组（P〈0.05）,损伤局部注射神经生长因子组次之。说明神经生长因子具有促进外周神经吻合后修复与再生的功能,鞘膜内应用优于局部注射。     

Upgraded Nerve Growth Factor Expression Induced by Low-Intensity Continuous-Wave Ultrasound Accelerates Regeneration of Neurotometicly Injured Sciatic Nerve in Rats

Low-intensity ultrasound (LIU) can stimulate injured nerve regeneration but the mechanism is still unclear. We investigated the stimulating effect and its mechanism of continuous-wave LIU on neurotometic injury of sciatic nerve. The right sciatic nerves of 64 adult Wistar rats were first crushed and then exposed (32 rats) or sham-exposed (32 rats) to LIU at the crush site. The LIU had a spatial averaged and temporal averaged intensity of 0.25W/cm² operated at 1.0 MHz for 1 min every other day. At various stages (the second, fourth, sixth and eighth weeks) after LIU exposure, the sciatic nerve function index (SFI), the sensory nerve conduction velocity (SNCV), the expression of nerve growth factor (NGF) and sample histology were studied. It was found that the density of nerve fibers with myelin sheath, SFI, SNCV and NGF expression of the treatment group were higher than that of control group (p < 0.05). It has been determined that LIU treatment can accelerate the regeneration and functional recovery of neurotometic injured sciatic nerve at earlier stages after injury, the upgraded expression of NGF induced by LIU may be the primary mechanism of the acceleration effects. (E-mail: wangzhibiao@haifu.com.cn)     

神经肽类物质与牙周支持组织及口腔骨修复

背景：随着对牙周病病因学和神经内分泌研究的深入,神经内分泌因素在牙周病发病及组织修复中的作用成为当今研究的热点。目的：综述神经肽类物质对牙周支持组织的生物学作用,及神经损伤后牙周组织变化的情况。方法：以“神经肽,降钙素基因相关肽,P 物质,舒血管肠肽,神经肽 Y 和牙周组织”为中文关键词,以“Neuropeptide,Calcitonin gene related peptide,substance P,vasoactive intestinal peptide,neuropeptide Y,periodontal”为英文关键词,采用计算机检索CNKI数据库、万方数据库和PubMed数据库,选择有关各类神经肽对牙周支持组织影响的文章进行分析。结果与结论：降钙素基因相关肽、P物质、舒血管肠肽、神经肽Y等相关阳性神经纤维广泛分布在牙周支持组织中,当感觉神经受到损伤后肽能神经分布及神经肽的释放发生改变,作用到牙周支持组织内的的靶细胞,在牙槽骨的改建、牙周韧带及牙周组织免疫功能等各方面发挥作用,这表明神经内分泌因素与牙周组织的关系非常密切,但是,这些相关研究多集中在对正畸和骨折动物模型的研究方面,神经肽等神经递质对牙周病的影响及其具体的作用机制还需要进一步探索。     

Spatial distribution of nociceptive neuropeptide and nerve growth factor depletion in experimental diabetic peripheral nervous system

This study investigated the time-course of the nociceptive neuropeptide substance P and nerve growth factor (NGF), which facilitates substance P production, in lumbar and cervical dorsal root ganglia (DRG) of streptozotocin-induced diabetic rats. Levels of substance P and NGF were measured by radioimmunoassay and sandwich enzyme-linked immunosorbent assay, respectively, 2 months, 4 months and 8 months after induction of diabetes, and compared with age-matched non-diabetic control rats. At 2 months and 4 months, substance P and NGF levels were lower in the lumbar DRG of the diabetic rats than in controls. At 8 months, substance P and NGF were lower in both the lumbar and cervical DRG of the diabetic rats than in controls. These data demonstrate that a decrease in substance P levels in primary sensory neurons with NGF depletion occurs in an axonal length-dependent manner in diabetic rats, and that this decrease may be correlated with the duration of diabetes.     

感觉性和运动性神经膜细胞的培养研究

目的对感觉性和运动性神经来源的神经膜细胞进行培养和鉴定,并通过神经生长因子(NGF)的表达间接地研究两种细胞的差别,探讨对神经特异性再生的影响。方法立体显微镜下对SD乳鼠后根神经和股神经运动支进行取材,经2.5g/L胰蛋白酶+0.3g/LIV型胶原酶联合消化,用高糖型DMEM/F12(含100g/LCS)对感觉神经源性和运动神经源性的神经膜细胞进行培养,并经抗S100荧光组织化学染色鉴定。双抗体夹心间接ELISA法测量两种神经膜细胞培养基中NGF的表达。结果培养的两种神经膜细胞经荧光染色证明均为神经膜细胞,光镜观察并手工计数显示两种细胞纯度均超过95%,未见形态学差异,但NGF的表达量和表达模式差异均有显著性意义(F=45.3681,P=0.000)。结论本实验方法可以获得高纯度的感觉性和运动性神经源性神经膜细胞,两者的生物学功能有差异。     

Innervation of melanocytes in human skin

Communication between the nervous system and epidermal melanocytes has been suspected on the basis of their common embryologic origin and apparent parallel involvement in several disease processes, but never proven. In this study, confocal microscopic analysis of human skin sections stained with antibodies specific for melanocytes and nerve fibers showed intraepidermal nerve endings in contact with melanocytes. This intimate contact was confirmed by electron microscopy, which further demonstrated thickening of apposing plasma membranes between melanocytes and nerve fibers, similar to synaptic contacts seen in nervous tissue. Since many intraepidermal nerve fibers are afferent nerves that act in a "neurosecretory" fashion through their terminals, cultured human melanocytes were stimulated with calcitonin gene-related peptide (CGRP), substance P, or vasoactive intestinal peptide, neuropeptides known to be present in cutaneous nerves, to examine their possible functions in the epidermal melanin unit. CGRP increased DNA synthesis rate of melanocytes in a concentration- and time-dependent manner. Cell yields after 5 d were increased 25% compared with controls maintained in an otherwise optimized medium. Furthermore, stimulation by CGRP induced rapid and dose-dependent accumulation of intracellular cAMP, suggesting that the mitogenic effect is mediated by the cAMP pathway. These studies confirm and expand a single earlier report in an animal model of physical contact between melanocytes and cutaneous nerves and for the first time strongly suggest that the nervous system may exert a tonic effect on melanocytes in normal or diseased human skin.     

微囊化转染神经生长因子基因细胞移植在周围神经再生中的作用

目的探讨应用免疫隔离技术进行转染神经生长因子（NGF）基因的3T3细胞移植促进周围神经损伤后再生的可行性.方法采用海藻酸钠-聚赖氨酸-海藻酸钠（APA）微胶囊包埋NGF-3T3细胞并进行培养;制备坐骨神经横断损伤SD大鼠模型,96只SD大鼠随机分A组（微囊化NGF-3T3细胞组）、B组（空胶囊组）、C组（转染NGF的3T3细胞组）和D组（阴性对照组）.分别采用神经干动作电位（NAP）、神经传导速度（NCV）和坐骨神经功能指数（SFI）检测坐骨神经功能恢复情况.结果微囊化NGF-3T3细胞培养后保持活性和增殖能力,将具有分化潜能的大鼠嗜铬细胞瘤细胞与其共培养,7 d时细胞胞体分化成多边形或锥形,形成突起;培养10 d左右NGF分泌量最高,达269 pg/ml;培育50 d仍然保持在208 pg/ml.移植术后4、8及12周时,A组大鼠的NAP及NCV均大于B、C、D组（P＜0.05）,而B、C、D三组之间无显著性差异（P＞0.05）;A组大鼠的SFI恢复情况优于B、C、D组（P＜0.05）,而B、C、D三组之间无显著性差异（P＞0.05）.结论微囊化NGF-3T3细胞在体外培养一定时间后,仍保持增殖能力和生物活性,移植到大鼠周围神经损伤局部后可长时间存活,并通过持续分泌NGF起到促进周围神经修复的作用.     

Collateral sprouting in skin and sensory recovery after nerve injury in man

Two different modes of cutaneous sensory reinnervation are thought to be engaged following nerve injury: regenerative growth of the injured nerve and 'collateral sprouting' of neighboring intact nerves. Although both processes are well known from experimental preparations, there is little unequivocal documentation of collateral sprouting in human skin. We report here on 5 patients in whom at least partial recovery of sensation in the hand following traumatic or surgical nerve section was apparently based on collateral sprouting from nerves that had not themselves been injured. Two types of evidence are brought. In three of the cases a totally anesthetic region of skin at a distance from the site of injury was shown to recover sensitivity long before regenerating nerve fibers could have arrived, given the known rates of fiber outgrowth. In the remaining two cases, nerve blocks using local anesthetics were used to establish that the reinnervated skin was served by a nerve other than the injured one. Thus, collateral sprouting appears to contribute to cutaneous sensory recovery in man as well as in animals.     

Let-7 microRNAs Regenerate Peripheral Nerve Regeneration by Targeting Nerve Growth Factor

Peripheral nerve injury is a common clinical problem. Nerve growth factor (NGF) promotes peripheral nerve regeneration, but its clinical applications are limited by several constraints. In this study, we found that the time-dependent expression profiles of eight let-7 family members in the injured nerve after sciatic nerve injury were roughly similar to each other. Let-7 microRNAs (miRNAs) significantly reduced cell proliferation and migration of primary Schwann cells (SCs) by directly targeting NGF and suppressing its protein translation. Following sciatic nerve injury, the temporal change in let-7 miRNA expression was negatively correlated with that in NGF expression. Inhibition of let-7 miRNAs increased NGF secretion by primary cultured SCs and enhanced axonal outgrowth from a coculture of primary SCs and dorsal root gangalion neurons. In vivo tests indicated that let-7 inhibition promoted SCs migration and axon outgrowth within a regenerative microenvironment. In addition, the inhibitory effect of let-7 miRNAs on SCs apoptosis might serve as an early stress response to nerve injury, but this effect seemed to be not mediated through a NGF-dependent pathway. Collectively, our results provide a new insight into let-7 miRNA regulation of peripheral nerve regeneration and suggest a potential therapy for repair of peripheral nerve injury.     

分米波对大鼠再生神经NGF mRNA表达的影响

目的研究分米波对周围神经损伤后再生神经中神经生长因子(NGF)表达的影响。方法选用60只SD大鼠，随机分为实验组和对照组各30只，均于右侧坐骨神经中段切除5mm神经组织，硅胶管桥接神经缺损，形成神经再生室，实验组术后进行局部分米波辐射。于术后1，2，4和8周取材，行大体和光镜观察，并进行免疫组化检测及RT-PCR定量分析。结果实验组NGF阳性染色颗粒及积分光密度值(IOD)明显高于对照组。实验组各时间点再生神经纤维中NGFmRNA的含量均明显高于对照组(P＜0、01)，同一神经纤维中．NGF mRNA表达量近侧明显高于远侧(P＜0．05)。实验组再生神经纤维中NGF mRNA于术后1周即有表达，术后2～4周达到高峰，术后8周后开始下降。结论分米波能增加神经纤维中NGF mRNA的表达，促进周围神经再生。     

牙种植体与许旺细胞联合培养时脑源性神经营养因子及神经生长因子mRNA的表达

背景:许旺细胞很可能是促进骨整合种植牙周围神经再生的有效因子。目的:观察许旺细胞与牙种植体复合培养时脑源性神经营养因子与神经生长因子mRNA的表达,分析牙种植体与许旺细胞的相容性。方法:取成年犬发生Wallerian变性的坐骨神经,用酶消化法和差速贴壁法相结合培养许旺细胞,以1×108L-1浓度接种于喷钛砂酸蚀的牙种植体表面和培养皿。分别在细胞培养的第1,3,6,8,11天,以反转录-聚合酶链反应检测许旺细胞中脑源性神经营养因子与神经生长因子mRNA的表达。结果与结论:许旺细胞与牙种植体复合培养时,脑源性神经营养因子与神经生长因子的表达趋势与许旺细胞单独培养时相同,呈单峰型;但两种基因的表达水平高于许旺细胞单独培养组,且达到表达峰值的时间较早。提示喷钛砂酸蚀表面的牙种植体能够促进许旺细胞的基因表达,两者具有良好的相容性。     

牙种植体与许旺细胞联合培养时脑源性神经营养因子及神经生长因子mRNA的表达

背景：许旺细胞很可能是促进骨整合种植牙周围神经再生的有效因子。目的：观察许旺细胞与牙种植体复合培养时脑源性神经营养因子与神经生长因子mRNA的表达,分析牙种植体与许旺细胞的相容性。方法：取成年犬发生Wallerian变性的坐骨神经,用酶消化法和差速贴壁法相结合培养许旺细胞,以1×108L^-1浓度接种于喷钛砂酸蚀的牙种植体表面和培养皿。分别在细胞培养的第1,3,6,8,11天,以反转录-聚合酶链反应检测许旺细胞中脑源性神经营养因子与神经生长因子mRNA的表达。结果与结论：许旺细胞与牙种植体复合培养时,脑源性神经营养因子与神经生长因子的表达趋势与许旺细胞单独培养时相同,呈单峰型;但两种基因的表达水平高于许旺细胞单独培养组,且达到表达峰值的时间较早。提示喷钛砂酸蚀表面的牙种植体能够促进许旺细胞的基因表达,两者具有良好的相容性。     

Artemin induced functional recovery and reinnervation after partial nerve injury

Systemic artemin promotes regeneration of dorsal roots to the spinal cord after crush injury. However, it is unclear whether systemic artemin can also promote peripheral nerve regeneration, and functional recovery after partial lesions distal to the dorsal root ganglion (DRG) remains unknown. In the present investigation, male Sprague Dawley rats received axotomy, ligation, or crush of the L5 spinal nerve or sham surgery. Starting the day of injury, animals received intermittent subcutaneous artemin or vehicle across 2 weeks. Sensory thresholds to tactile or thermal stimuli were monitored for 6 weeks after injury. Immunohistochemical analyses of the DRG and nerve regeneration were performed at the 6-week time point. Artemin transiently reversed tactile and thermal hypersensitivity after axotomy, ligation, or crush injury. Thermal and tactile hypersensitivity reemerged within 1 week of treatment termination. However, artemin-treated rats with nerve crush, but not axotomy or ligation, subsequently showed gradual return of sensory thresholds to preinjury baseline levels by 6 weeks after injury. Artemin normalized labeling for NF200, IB4, and CGRP in nerve fibers distal to the crush injury, suggesting persistent normalization of nerve crush-induced neurochemical changes. Sciatic and intradermal administration of dextran or cholera toxin B distal to the crush injury site resulted in labeling of neuronal profiles in the L5 DRG, suggesting regeneration functional restoration of nonmyelinated and myelinated fibers across the injury site into cutaneous tissue. Artemin also diminished ATF3 and caspase 3 expression in the L5 DRG, suggesting persistent neuroprotective actions. A limited period of artemin treatment elicits disease modification by promoting sensory reinnervation of distal territories and restoring preinjury sensory thresholds.     

Peptides and vasomotor mechanisms

The multiple and diverse roles played by neuropeptide Y, vasoactive intestinal polypeptide, substance P, calcitonin gene-related peptide and other biologically active peptides in the cardiovascular system are considered. A model of the vascular neuroeffector junction is described, which illustrates the interactions of peptidergic and nonpeptidergic transmitters that are possible at pre- and postjunctional sites. The effects of peptides on specific endothelial receptors are also described, which highlights the ability of these agents to act as dual regulators of vascular tone at both adventitial and intimal surfaces, following local release from nerves, or from endothelial cells themselves. Changes in expression of vascular neuropeptides that occur during development and aging in some disease situations and following nerve lesion are discussed.     

神经生长因子对挤压伤坐骨神经再生的促进作用

背景神经生长因子(nerve growth factor,NGF)不仅是维持促进中枢神经系统发育、分化、存活的基本的生长因子,而且在外周神经损伤的修复中也起着重要的作用.目的观察NGF肌注对大鼠坐骨神经挤压伤后神经再生恢复以及功能的影响.设计以实验动物为研究对象,随机对照的重复观察测量,探索性研究.单位一所军医大学的新药评价中心.材料实验于1999-07/2000-03在第二军医大学基础部新药评价中心完成.SD大鼠40只,雌雄各半,体质量200～250 g,上海西普尔-必凯实验动物有限公司提供.方法将40只大鼠随机分成NGF高、中、低剂量组,正常对照和模型对照组.距坐骨切迹远端6 mm处钳夹坐骨神经,使产生-4 mm宽的挤压伤.NGF高、中、低剂量组分别给予NGF 8,4和2μg/kg(1.6×103,8×102和4×102 IU/kg)药物,肌注1次/d,连续56 d.主要观察指标①手术后的不同时间神经传导速度(nerve conduction ve1ocities,NCV)和坐骨神经功能指数(sciatic functional index,SFI).②组织形态学评价.结果与模型对照组相比,高剂量组在35,56 d,中剂量组在35 d的NCV均显著加快(t=2.32～5.14,P＜0.05～0.01);高、中、低3个剂量组在手术14 d后的SFI与模型组相比,差异均有显著性意义(t=2.29～6.28,P＜0.05～0.01),且高剂量组恢复较明显,至56 d各剂量组SFI各组差异均无显著性意义;组织形态学显示,NGF治疗组神经髓鞘、轴索与正常对照组相比,差异无显著性意义;而模型组髓鞘出现脱失,细微结构不清晰,许旺细胞变性坏死.结论NGF对大鼠坐骨神经受损部位的神经髓鞘及轴索有明显的改善作用,能促进其神经纤维的再生及神经功能的恢复.     

神经生长因子促进再生坐骨神经中血管生成的量效关系

背景:对于神经生长因子的促血管生成作用的研究,目前还处于探索阶段。目的:探讨神经生长因子对再生坐骨神经中血管形成的剂量效应及其机制。设计:随机对照动物实验。单位:解放军第三二四医院神经内科,解放军第三军医大学大坪医院野战外科研究所三室。材料:健康成年Wistar大鼠32只,雌雄不拘,体质量200～250g。硅胶管(上海新亚医用橡胶厂出产);神经生长因子(美国Sigma公司)。方法:实验于2003-08/2005-02在解放军第三军医大学大坪医院野战外科研究所三室完成。实验分组:采用随机数字法将大鼠分成4组:生理盐水组、50,100,500ng神经生长因子组,每组8只。实验干预:切除大鼠后肢坐骨神经,造成10mm缺损,用单通道的硅胶管桥接大鼠坐骨神经缺损,在桥接管内给药。生理盐水组注入5μL生理盐水。50,100,500ng神经生长因子组注入20mg/L的神经生长因子2.5,5,25μL。实验评估:在第30天时,用免疫组织化学的方法检测大鼠再生坐骨神经新生血管内皮细胞中CD34、vWf、血管内皮生长因子、trkA的表达,并作形态计量分析。主要观察指标:各组大鼠神经再生普通病理及组织化学染色观察。结果:32只大鼠全部进入结果分析。①各组大鼠神经再生病理切片结果:术后30d的坐骨神经近远端完全连接,硅胶管内坐骨神经粗壮程度为:500ng神经生长因子组>50ng、100ng组>生理盐水组。各神经生长因子组再生的坐骨神经的纤维数目和排列规则程度要好于生理盐水组,术后30d可见明显的血管生成。②免疫组织化学染色观察:3种不同剂量的神经生长因子组与生理盐水组比较,4种抗原的表达皆有显著性差异(P<0.05);500ng神经生长因子组4种抗原的表达与100ng和50ng神经生长因子组比较增加(CD34:94.2±6.4,74.2±10.9,77.0±11.0;vWf:116.2±20.0,72.0±13.1,68.0±9.7;TrkA:105.4±10.6,57.8±11.5,58.8±6.5;血管内皮生长因子:89.0±3.0,48.6±7.4,35.2±2.9;P<0.05或P<0.01)。结论:神经生长因子能促进再生周围神经的血管生成,且具有剂量效应;其机制可能与神经生长因子促进trkA、血管内皮细胞生长因子的表达密切相关。     

The trk family of receptors mediates nerve growth factor and neurotrophin-3 effects in melanocytes.

We have recently shown that (a) human melanocytes express the p75 nerve growth factor (NGF) receptor in vitro; (b) that melanocyte dendricity and migration, among other behaviors, are regulated at least in part by NGF; and (c) that cultured human epidermal keratinocytes produce NGF. We now report that melanocyte stimulation with phorbol 12-tetra decanoate 13-acetate (TPA), previously reported to induce p75 NGF receptor, also induces trk in melanocytes, and TPA effect is further potentiated by the presence of keratinocytes in culture. Moreover, trk in melanocytes becomes phosphorylated within minutes after NGF stimulation. As well, cultures of dermal fibroblasts express neurotrophin-3 (NT-3) mRNA; NT-3 mRNA levels in cultured fibroblasts are modulated by mitogenic stimulation, UV irradiation, and exposure to melanocyte-conditioned medium. Moreover, melanocytes constitutively express low levels of trk-C, and its expression is downregulated after TPA stimulation. NT-3 supplementation to cultured melanocytes maintained in Medium 199 alone prevents cell death. These combined data suggest that melanocyte behavior in human skin may be influenced by neurotrophic factors, possibly of keratinocyte and fibroblast origin, which act through high affinity receptors.     

HSV-mediated gene transfer of vascular endothelial growth factor to dorsal root ganglia prevents diabetic neuropathy

We examined the utility of herpes simplex virus (HSV) vector-mediated gene transfer of vascular endothelial growth factor (VEGF) in a mouse model of diabetic neuropathy. A replication-incompetent HSV vector with VEGF under the control of the HSV ICP0 promoter (vector T0VEGF) was constructed. T0VEGF expressed and released VEGF from primary dorsal root ganglion (DRG) neurons in vitro, and following subcutaneous inoculation in the foot, expressed VEGF in DRG and nerve in vivo. At 2 weeks after induction of diabetes, subcutaneous inoculation of T0VEGF prevented the reduction in sensory nerve amplitude characteristic of diabetic neuropathy measured 4 weeks later, preserved autonomic function measured by pilocarpine-induced sweating, and prevented the loss of nerve fibers in the skin and reduction of neuropeptide calcitonin gene-related peptide and substance P in DRG neurons of the diabetic mice. HSV-mediated transfer of VEGF to DRG may prove useful in treatment of diabetic neuropathy.     

人胚雪旺细胞组织工程神经修复坐骨神经缺损的实验研究

目的：探索人胚雪旺细胞作为组织工程的种子细胞修复周围神经缺损的可行性。方法：通过组织工程方法用PLGA导管和polyglactin 910纤维负载人胚雪旺细胞预先构置好人工神经，然后用于修复大鼠20mm的坐骨神经缺损，并与神经切断后原位缝合以及用单纯的PLGA导管进行修复的实验组进行对照。通过活体肢体功能观察、靶器官肌肉测量、电生理检测、辣根过氧化物酶示踪、连续组织切片图像分析以及透射电镜等检查神经再生情况。结果：人工神经修复组神经再生良好，效果接近于神经原位缝合组，明显优于单纯的PLGA导管修复组。结论：人胚雪旺细胞构建的人工神经可以修复20mm的周围神经缺损。     

Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation

Neurogenic inflammation is believed to originate with the antidromic release of substance P, and of other neurokinins encoded by the preprotachykinin A (PPT-A) gene, from unmyelinated nerve fibers (C-fibers) following noxious stimuli. Consistent with this concept, we show here that selective sensory-fiber denervation with capsaicin and targeted deletion of the PPT-A gene protect murine lungs against both immune complex-mediated and stretch-mediated injuries. Reconstitution of PPT-A gene-deleted mice with WT bone marrow does not abrogate this protection, demonstrating a critical role for PPT-A gene expression by sensory neurons in pulmonary inflammation. Surprisingly, reconstitution of WT mice with PPT-A gene-deficient bone marrow also confers protection against pulmonary injury, revealing that PPT-A gene expression in hemopoietic cells has a previously unanticipated essential role in tissue injury. Taken together, these findings demonstrate a critical synergy between capsaicin-sensitive sensory fibers and hemopoietic cells in neurokinin-mediated inflammation and suggest that such synergy may be the basis for a stereotypical mechanism of response to injury in the respiratory tract.