RESUMEN
The purposes of this study were to clarify whether damage of the nasal epithelium exists in patients with nasal allergy, and how the morphology of the epithelium changes after topical allergen challenge. Electron microscopy revealed 2 characteristic features in the nasal epithelium of patients with perennial nasal allergy--an increase in the number of epithelial cells with cytoplasmic vacuoles, and markedly widened intercellular spaces--although these changes were unclear under light microscopy. The density of vacuolated cells significantly increased 24 hours after allergen challenge. Further, the number of eosinophils that were associated with vacuolated cells was significantly higher in patients with nasal allergy than in controls. These morphological changes, thus, were considered to be types of damage to the nasal epithelium associated with nasal allergy. Such changes may be among the causes of nasal hyperreactivity, which is an important feature of nasal allergy.
Asunto(s)
Alérgenos/administración & dosificación , Nariz/patología , Rinitis Alérgica Perenne/patología , Administración Tópica , Adolescente , Adulto , Epitelio/patología , Humanos , Microscopía ElectrónicaRESUMEN
The time course of changes in absorption of horseradish peroxidase (HRP) through the nasal mucosa after antigen challenge was evaluated in a guinea pig model of allergic rhinitis immunized with ovalbumin. Before and at 5 minutes, 4 hours, and 24 hours after nasal antigen challenge, both nasal cavities were filled with 5% HRP solution for 30 minutes, and blood was obtained to measure serum HRP levels by enzyme-linked immunosorbent assay. In immunized animals, the serum HRP levels were 2.3 times higher than those of normal controls (p<.05) before antigen challenge, which was performed 7 days after a series of nasal antigenic sensitizations. At 5 to 35 minutes after antigen challenge, the HRP levels decreased to one sixth of the prechallenge levels (p<.05), and they did not show a difference from the control levels. However, they increased markedly at 4 and 24 hours after antigen challenge (p<.01). The present study suggests that the absorption of macromolecules through the allergic nasal mucosa is enhanced markedly, depending upon the time course after antigen challenge, although it shows no apparent difference from normal controls during the dominant exudative process.
Asunto(s)
Modelos Animales de Enfermedad , Peroxidasa de Rábano Silvestre/sangre , Peroxidasa de Rábano Silvestre/farmacocinética , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/inmunología , Pruebas de Provocación Nasal , Rinitis Alérgica Estacional/sangre , Rinitis Alérgica Estacional/inmunología , Absorción , Animales , Permeabilidad de la Membrana Celular/efectos de los fármacos , Permeabilidad de la Membrana Celular/inmunología , Ensayo de Inmunoadsorción Enzimática , Cobayas , Inyecciones Intraperitoneales , Masculino , Pruebas de Provocación Nasal/métodos , Ovalbúmina , Rinitis Alérgica Estacional/inducido químicamente , Factores de TiempoRESUMEN
BACKGROUND: The literature on abnormality of vasomotor responses of the nasal mucosa to cold stimulation of the skin in idiopathic rhinitis is conflicting. The objective of this study was to elucidate pathophysiological features of the nasal mucosa in idiopathic rhinitis compared to allergic rhinitis. METHODS: The following were studied in patients with idiopathic rhinitis and allergic rhinitis and in normal controls: (1) threshold of the nasal reaction to histamine; (2) inflammatory cells in nasal lavage and scraped nasal mucosal epithelium, and (3) nasal vasomotor response to cold stimulation of the feet evaluated by acoustic rhinometry. RESULTS: Inflammatory cells were not found to be involved in idiopathic rhinitis. Nasal reactivity to histamine was significantly enhanced in patients with idiopathic rhinitis compared to normal controls, but was significantly lower compared to those with allergic rhinitis. The most prominent finding in idiopathic rhinitis was nasal mucosal swelling induced by cold stimulation of the feet. While in normal controls, cold stimulation of the feet caused mucosal contraction due to sympathetic excitation, sympathetic nasal vasomotor response in idiopathic rhinitis patients was significantly inhibited and caused mucosal swelling and enhanced nasal secretion. Mucosal reactions observed in allergic rhinitis were between those observed in idiopathic rhinitis and in normal controls. Cold stimulation of the feet increased systolic blood pressure by 5-15 mm Hg, but the degree of increase observed in the 3 groups was almost equal. CONCLUSIONS: The above findings indicate that patients with idiopathic rhinitis have abnormalities that inhibit sympathetic reactions and enhance parasympathetic vasomotor response at peripheral levels, possibly in the nasal mucosa.
Asunto(s)
Mucosa Nasal/fisiopatología , Rinitis Alérgica Perenne/fisiopatología , Rinitis Vasomotora/fisiopatología , Adolescente , Adulto , Edad de Inicio , Aire , Presión Sanguínea , Frío , Eosinófilos/patología , Células Epiteliales/patología , Femenino , Histamina/farmacología , Humanos , Recuento de Leucocitos , Masculino , Líquido del Lavado Nasal/química , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , Rinitis Alérgica Perenne/metabolismo , Rinitis Alérgica Perenne/patología , Rinitis Vasomotora/metabolismo , Rinitis Vasomotora/patología , Estornudo/inmunologíaRESUMEN
Neutrophil emigration in response to acid aspiration does not require the adhesion complex, CD11/ CD18. This study examined the role of CD11b/CD18 using the anti-CD11b F(ab')2, 1B6, in focal HCI-induced intracapillary neutrophil sequestration and edema formation within rat lungs, as well as the effect of pretreatment with endotoxin on this injury. The results show that at the site of aspiration pneumonia, anti-CD11b F(ab')2 did not inhibit neutrophil sequestration or edema formation, either with or without endotoxin pretreatment. In the contralateral lung, focal HCI aspiration induced neutrophil sequestration that was inhibited by the anti-CD11b F(ab')2, but no edema formation. The combined effect of endotoxin pretreatment and HCI aspiration induced CD11b/CD18-independent edema formation in the contralateral lung. These data indicate that CD11b/CD18-independent pathways mediate neutrophil sequestration and edema formation at that pneumonic site with or without pretreatment with endotoxin. CD11b/CD18 mediates neutrophil sequestration at distant sites when no endotoxin is present, although this CD11b/CD18-dependent sequestration is not association with edema formation. The combined effects of endotoxin and HCI aspiration induce edema formation at distant sites that could not be prevented by inhibiting the function of the CD11b/CD18 prior to aspiration.
Asunto(s)
Antígenos CD18/inmunología , Adhesión Celular/inmunología , Movimiento Celular/inmunología , Antígeno de Macrófago-1/inmunología , Activación Neutrófila/inmunología , Neumonía por Aspiración/inmunología , Animales , Modelos Animales de Enfermedad , Endotoxinas , Ácido Clorhídrico , Inflamación , Recuento de Leucocitos , Neumonía por Aspiración/sangre , Neumonía por Aspiración/inducido químicamente , Premedicación , Ratas , Ratas Sprague-DawleyRESUMEN
Complement fragment-induced sequestration of neutrophils within the lungs may be mediated by stimulus-induced decreases in the deformability of neutrophils, prolonging their lung capillary transit times. As changes in deformability often occur through changes in cytoskeletal proteins, this study determined whether the distribution of actin within intracapillary neutrophils was altered by intravascular complement fragments and whether sequestered neutrophils were less deformed. Ultrathin cryosections of lung tissue from rabbits given an infusion of complement fragments or saline were immunolabeled with anti-actin antibodies. The number of gold particles/microvillus and the density of gold particles/microgram 2 cytoplasm in the submembrane and the central region of intracapillary neutrophils was quantitated. Neutrophil shape was evaluated using laser confocal microscopy. In control rabbits, the ratio of submembrane/central gold was always greater than one and most neutrophils were elongated, 97% having shape factors > 1.10. The ratio of submembrane/central gold was greater in complement-treated rabbits (5.1 +/- 0.9) than controls (2.6 +/- 0.4; P < 0.026). The number of gold particles/microvillus was also increased in complement-treated rabbits (3.9 +/- 0.5) compared with controls (2.3 +/- 0.5; P < 0.045). Neutrophils were more often spherical when rabbits received complement fragments for 1.5 minutes than in control lungs or after 15-minute infusions. These data suggest that complement fragments induce a rapid redistribution of actin from the central to the submembrane region and the microvilli and result in more round neutrophils. This redistribution may decrease the deformability of neutrophils by altering the stiffness of the submembrane region and/or by preventing the microvilli from flattening.
Asunto(s)
Actinas/metabolismo , Proteínas del Sistema Complemento/fisiología , Neutrófilos/fisiología , Fagocitosis/fisiología , Actinas/análisis , Actinas/ultraestructura , Animales , Tamaño de la Célula/efectos de los fármacos , Proteínas del Sistema Complemento/farmacología , Inmunohistoquímica , Recuento de Leucocitos/efectos de los fármacos , Activación Neutrófila , Neutrófilos/química , Péptidos/farmacología , ConejosRESUMEN
The effects of topically administered substance P (SP) on nasal blood flow and nasal airway resistance (NAR) were evaluated in 11 subjects with perennial nasal allergy. The change in NAR induced by SP was compared with those induced by nasal challenge with histamine, leukotriene D4 (LTD4), and antigen. In doses > or = 16 nmol, SP caused a significant increase of nasal blood flow within 5 minutes that lasted for less than 20 minutes. In doses > or = 16 nmol, SP caused a dose-dependent, short-lasting, significant increase in NAR. The magnitude of the increase in NAR was LTD4 > SP > histamine when compared on a molar basis. Our results may suggest that SP released from C fiber terminals is partially involved in an early nasal vascular response after antigen challenge by acting on adjacent vascular smooth muscle to cause a transient vasodilatation of both resistance and capacitance vessels only while sensory stimulation persists in subjects with nasal allergy.
Asunto(s)
Mucosa Nasal/fisiopatología , Rinitis Alérgica Perenne/fisiopatología , Sustancia P/fisiología , Adolescente , Adulto , Resistencia de las Vías Respiratorias , Antígenos/farmacología , Femenino , Histamina/farmacología , Humanos , Leucotrieno D4/farmacología , Masculino , Mucosa Nasal/irrigación sanguínea , Mucosa Nasal/efectos de los fármacos , Sustancia P/farmacologíaRESUMEN
The effect of capsaicin pretreatment on frequency of sneezing, decrease of nasal patency, and increase of vascular dye leakage induced by antigen or histamine challenge on the guinea pig nasal mucosa was investigated. The animals were sensitized intraperitoneally with ovalbumin. Capsaicin pretreatment significantly inhibited sneezing induced by nasal challenge with histamine and antigen, indicating that capsaicin-sensitive sensory nerves constitute an afferent pathway of the sneezing reflex in nasal allergy. Although capsaicin pretreatment tended to inhibit the decrease of nasal patency and the increase of vascular dye leakage of the nasal mucosa induced by antigen challenge, this tendency was not statistically significant. The present study indicated that the participation of a local reflex via capsaicin-sensitive trigeminal nerves in nasal vascular responses observed after antigen challenge in the guinea pig model of nasal allergy is rather small compared to the large direct vascular effects of chemical mediators released from basophilic cells in the nasal mucosa.
Asunto(s)
Capsaicina/farmacología , Hipersensibilidad/fisiopatología , Mucosa Nasal/fisiología , Nervio Trigémino/fisiología , Resistencia de las Vías Respiratorias/efectos de los fármacos , Resistencia de las Vías Respiratorias/fisiología , Animales , Cobayas , Inmunización , Masculino , Mucosa Nasal/irrigación sanguínea , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/inervación , Estornudo/efectos de los fármacos , Estornudo/fisiología , Nervio Trigémino/efectos de los fármacosRESUMEN
Nasal mucosa was investigated by NADPH-diaphorase histochemistry. Positive fibers were distributed around blood vessels, seromucous glands and in the subepithelial layer. The pterygopalatine, trigeminal and superior cervical ganglia were also studied to examine the origin of these fibers. Many neurons in the pterygopalatine ganglion were labeled, and a few neurons were stained in the trigeminal ganglion. No perikarya were labeled in the superior cervical ganglion. Therefore, most of the labeled fibers must be originating from the pterygopalatine ganglion, and the rest of them may originate from the trigeminal ganglion. These results suggest that nitric oxide may have some role in the nervous control of the nasal mucosa.
Asunto(s)
NADPH Deshidrogenasa/metabolismo , Mucosa Nasal/inervación , Fibras Nerviosas/enzimología , Animales , Ganglios/citología , Ganglios/enzimología , Masculino , Mucosa Nasal/enzimología , Ratas , Ratas Sprague-Dawley , Ganglio Cervical Superior/citología , Ganglio Cervical Superior/enzimología , Ganglio del Trigémino/citología , Ganglio del Trigémino/enzimologíaRESUMEN
Immunohistochemical studies were performed to determine the distribution of neuropeptides and tyrosine hydroxylase in rat and human pterygopalatine ganglia. In the rat pterygopalatine ganglion, the most commonly found peptide in ganglion cells was vasoactive intestinal polypeptide (VIP) (99%) followed by neuropeptide Y (NPY) (54%) and enkephalin (ENK) (11%). Substance P (SP)-, calcitonin gene-related peptide (CGRP)-, ENK-, and NPY-immunoreactive (IR) varicose nerve fibers were found around ganglion cells. SP- and CGRP-IR varicosities were in synaptic contact with somatic spines or somata of ganglion cells. The combination of retrograde labeling and immunohistochemical study revealed that some of the ganglion cells projecting to the nasal mucosa were surrounded by SP-IR fibers. These results indicate that SP- and CGRP-IR axon collaterals of the trigeminal ganglion cells may form direct synaptic contact with ganglion cells projecting to the nasal mucosa. ENK-IR varicosities were probably derived from parasympathetic preganglionic neurons. In the human pterygopalatine ganglion, almost all ganglion cells were VIP-IR. They were not, however, immunoreactive with other peptides investigated in this study. VIP-, SP- and CGRP-IR varicose nerve fibers were found around ganglion cells. A few NPY- and ENK-IR varicose fibers were also observed around ganglion cells. The origins of these peptide-IR varicose nerve fibers are still unknown, but it is suggested that the human pterygopalatine ganglion is innervated by a greater variety of peptide-IR nerve fibers than that of the rat and forms different neuronal circuit.
Asunto(s)
Ganglios Parasimpáticos/metabolismo , Neurotransmisores/metabolismo , Animales , Humanos , Inmunohistoquímica , Masculino , Hueso Paladar/inervación , Ratas , Ratas Sprague-Dawley , Péptido Intestinal Vasoactivo/metabolismoRESUMEN
The distribution and quantity of neuropeptides in the rat pterygopalatine ganglion were studied by using complete serial paraffin sections of the ganglion immunostained with antiserum against several neuropeptides. The pterygopalatine ganglion, composed of 4932 +/- 291 (mean +/- SD) neurons, was triangular in shape with a tapering caudal tail. The most commonly found peptide in neurons was vasoactive intestinal polypeptide (VIP) (99.0%), followed by neuropeptide Y (NPY) (54.1%) and enkephalin (10.5%). The rostro-ventromedial and caudal parts of the ganglion where intensely VIP-immunoreactive neurons predominate project to the nasal mucosa, while the rostro-dorsolateral part of the ganglion where NPY-immunoreactive neurons predominate projects to the Harderian gland. The coexistence of VIP/NPY (47.4%), VIP/NPY/enkephalin (6.6%) or VIP/enkephalin (3.9%) in the ganglionic neurons was recognized. Calcitonin gene-related peptide (CGRP)- and substance P-immunoreactive varicosities formed synaptic contacts with the somatic spine or soma, which confirmed that the reflex arch, composed of axon collaterals of trigeminal ganglionic neurons and parasympathetic ganglionic neurons, operates through direct synapses. Enkephalin-immunoreactive varicosities, which were probably derived from parasympathetic preganglionic neurons, also made synaptic contact with the somatic spine.