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Biomedical subjects

E Y Chi

Publications and source records attributed to E Y Chi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Influence of the route of allergen administration and genetic background on the murine allergic pulmonary response.

We used various ovalbumin sensitization and challenge protocols to determine the importance of the route of allergen administration and the genetic background in modulating the physiologic, inflammatory, and immunologic features characteristic of allergen-induced asthma. In BALB/c mice, induction of maximal airway hyperresponsiveness and airspace eosinophilia required administration of ovalbumin by both the intraperitoneal and the intranasal routes (combination protocol), whereas intraperitoneal immunization alone resulted in maximal ovalbumin-specific IgE plasma levels. Thus, a systemic immune response to allergen, in addition to, or independent of IgE production, as well as local allergen challenge were necessary for maximal induction of pulmonary disease. BALB/c mice treated with ovalbumin by the combination protocol had increased Th2-type cytokine mRNA levels in bronchial lymph node tissue compared with control mice. In contrast, C57BL/6 mice treated with ovalbumin by the combination protocol had significantly decreased responses compared with BALB/c mice for all parameters of allergic pulmonary disease examined, with the exception of airspace eosinophilia. Genetic background has a striking and selective effect on the phenotype of murine allergic pulmonary disease. Further analysis of this murine model should be useful in helping define the critical pathogenetic events in allergen-induced asthma.

Administration, Intranasal↗
PubMed1997

Pulmonary and systemic inflammatory responses in rabbits with gram-negative pneumonia.

The major goals of this study were to define the relationships between intrapulmonary and systemic inflammatory responses in animals with gram-negative pneumonia. We treated rabbits with intrapulmonary Escherichia coli (1 x 10(7) to 1 x 10(10) cfu/ml), and then measured physiologic, cellular, and molecular events in the lungs and systemic circulation for 24 h. The treatment protocols resulted in groups of animals that mimicked the stages of the septic inflammatory response in humans. Animals treated with low inocula had systemic changes consistent with systemic inflammatory response syndrome and cleared the bacteria and inflammatory products from the lungs. Animals treated with high inocula failed to clear bacteria from the lungs, had severe intrapulmonary inflammatory responses, and developed septic shock. Intrapulmonary leukocyte recruitment was directly related to the size of the bacterial inoculum, but lung protein accumulation was not. Tumor neurosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and GRO were detectable in lung lavage fluid at 4 h and declined by 24 h in animals that cleared intrapulmonary E. coli. In contrast, lavage TNF-alpha, IL-8, and GRO increased over 24 h in animals that failed to clear intrapulmonary bacteria. MCP-1 increased between 4 h and 24 h in the lungs of all of the animals as the histologic response evolved from neutrophilic to mononuclear cell predominance. Thus, the intensity of systemic inflammatory and physiologic responses to intrapulmonary gram-negative infection depends on the inoculum size and whether the bacteria are cleared from or proliferate in the lungs. The results provide experimental support for the recently proposed classification of septic responses in humans.

Animals↗
PubMed1997

Neutrophil apoptosis in the acute respiratory distress syndrome.

Little is known about neutrophil (PMN) apoptosis in the acute respiratory distress syndrome (ARDS). We uses morphologic criteria to count apoptotic PMN in bronchoalveolar lavage fluid (BAL) of 35 patients on Days 1, 3, 7, 14, and 21 of ARDS and 13 patients on Days 1 and 3 of risk for ARDS. We found that the proportion of apoptotic PMN in BAL was low throughout the course of ARDS. There was no significant difference between the percentage of apoptotic PMN in patients at risk and patients with established ARDS or between patients who lived (2.4%) and patients who died (1.8%). When normal human PMN were incubated in ARDS BAL, a significantly lower proportion became apoptotic (50 +/- 4%), as compared with PMN incubated in lavage fluid from normal volunteers (76 +/- 7%, p < 0.05). This antiapoptotic effect of ARDS BAL was blocked by immunodepleting BAL of G-CSF and GM-CSF. We conclude that the proportion of apoptotic PMN recovered from the lungs of patients with ARDS is low throughout the course of ARD S. Furthermore, BAL from patients with ARDS prolongs survival of normal human PMN in vitro, and this effect is partially mediated by G-CSF and GM-CSF.

Adult↗
PubMed1996

The importance of leukotrienes in airway inflammation in a mouse model of asthma.

Inhalation of antigen in immunized mice induces an infiltration of eosinophils into the airways and increased bronchial hyperreactivity as are observed in human asthma. We employed a model of late-phase allergic pulmonary inflammation in mice to address the role of leukotrienes (LT) in mediating airway eosinophilia and hyperreactivity to methacholine. Allergen intranasal challenge in OVA-sensitized mice induced LTB4 and LTC4 release into the airspace, widespread mucus occlusion of the airways, leukocytic infiltration of the airway tissue and broncho-alveolar lavage fluid that was predominantly eosinophils, and bronchial hyperreactivity to methacholine. Specific inhibitors of 5-lipoxygenase and 5-lipoxygenase-activating protein (FLAP) blocked airway mucus release and infiltration by eosinophils indicating a key role for leukotrienes in these features of allergic pulmonary inflammation. The role of leukotrienes or eosinophils in mediating airway hyperresponsiveness to aeroallergen could not be established, however, in this murine model.

5-Lipoxygenase-Activating Proteins↗
PubMed1996

Ultrastructural characterization of preosteoclasts derived from bone marrow progenitors stimulated by osteoclast colony stimulating factor.

BACKGROUND: Osteoclast colony stimulating factor (O-CSF) is an osteoclast-specific growth factor that stimulates the clonal growth of primitive osteoclast progenitors from bone marrow cells in culture. To characterize the morphology of immature osteoclasts (preosteoclasts) arising from complex hematopoietic tissues, progenies of O-CSF-responsive progenitors were cocultured with devitalized calvariae, and their cytochemical and ultrastructural features were examined. METHODS: Murine bone marrow cells were cultured in semisolid medium for 14 days in the presence of O-CSF. Colonies derived from osteoclast progenitors were then cocultured with devitalized mouse calvariae for 5 days. Cells attached to the calvariae were stained for tartrate resistant acid phosphatase (TRAPase), and the ultrastructure of these cells was examined by transmission electron microscopy. Bone marrow cells stimulated by macrophage colony stimulating factor (M-CSF) were similarly studied as a control. RESULTS: O-CSF-induced preosteoclasts stained strongly positive for TRAPase when cocultured with calvariae. These cells showed single nuclei, and their cytoplasm contained numerous mitochondria, vacuoles, granules, and coated vesicles. The ruffled cell border consisted of short, blunt, fingerlike projections. The adjacent clear zone contained abundant microtubules, microfilaments, and long narrow channels. M-CSF-induced macrophages were TRAPase negative, with no ruffled borders or clear zones. CONCLUSIONS: All the characteristic features of active osteoclasts were observed in the cells derived from O-CSF-responsive bone marrow progenitors except that these cells were mononucleated, and their ruffled borders were not fully convoluted, indicative of their immature nature. This study documents for the first time the ultrastructural characteristics of preosteoclasts derived from cultured bone marrow progenitors in early stages of development.

Acid Phosphatase↗
PubMed1996

Invasion of respiratory epithelial cells by Burkholderia (Pseudomonas) cepacia.

Pulmonary infections caused by Burkholderia (Pseudomonas) cepacia are an important cause of morbidity and mortality in cystic fibrosis (CF) patients. Several features suggestive of cellular invasion and intracellular sequestration of B. cepacia in CF are persistence of infection in the face of antibiotic therapy to which the organism demonstrates in vitro susceptibility and a propensity to cause bacteremic infections in patients with CF. Epithelial cell invasion was demonstrated in vitro in A549 cells by a modified gentamicin protection assay. The kinetics of invasion appear to be saturable. Electron microscopy of invaded monolayers showed intracytoplasmic bacteria enclosed by membrane-bound vacuoles. No lysosomal fusion with these vacuoles was observed. Intraepithelial cell replication was suggested by electron microscopy and confirmed by both a quantitative assay and a visual assay. Cytochalasin D, but not colchicine, inhibited invasion, suggesting a role for microfilaments but not microtubules. The invasion phenotype in B. cepacia may be an important virulence factor for CF infections.

Burkholderia Infections↗
PubMed1996

Group B streptococcal beta-hemolysin expression is associated with injury of lung epithelial cells.

Group B streptococci (GBS) are the leading cause of serious bacterial infection in newborns. Early-onset disease is heralded by pneumonia and lung injury, and the lung may serve as a portal of entry for GBS into the bloodstream. To examine a potential role for GBS beta-hemolysin in lung epithelial injury, five wild-type strains varying in beta-hemolysin expression were chosen, along with five nonhemolytic (NH) and five hyperhemolytic (HH) variants of these strains derived by chemical or transposon mutagenesis. Monolayers of A549 alveolar epithelial cells were exposed to log-phase GBS or stabilized hemolysin extracts of GBS cultures, and cellular injury was assessed by lactate dehydrogenase (LDH) release and trypan blue nuclear staining. Whereas NH strains produced no detectable injury beyond baseline (medium alone), hemolysin-producing strains induced LDH release from A549 cells in direct correlation to their ability to lyse sheep erythrocytes. HH strains were also associated with marked increases in trypan blue nuclear staining of A549 monolayers. The extent of LDH release produced by HH strains was significantly reduced in the presence of dipalmitoyl phosphatidylcholine, a known inhibitor of hemolysin and the major phospholipid component of human surfactant. Electron microscopic studies of A549 cell monolayers exposed to HH GBS mutants revealed global loss of microvillus architecture, disruption of cytoplasmic and nuclear membranes, and marked swelling of the cytoplasm and organelles. We conclude that GBS hemolysin expression correlates with lung epithelial cell injury and may be important in the initial pathogenesis of early-onset disease, particularly when pulmonary surfactant is deficient.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

CD18-independent mechanism of neutrophil emigration in the rabbit lung after ischemia-reperfusion.

BACKGROUND: Reperfusion of ischemic lung causes an inflammatory pulmonary vascular injury characterized by increased vascular permeability and migration of inflammatory cells into the alveoli. Migration of neutrophils into the alveolus during reperfusion after 24 hours of unilateral pulmonary artery occlusion has been shown to be in part dependent on the CD18 adhesion molecule on the cell surface. The current study investigated whether reperfusion lung injury after a 1-hour period of complete lung ischemia was CD18 dependent. METHODS: Eighteen rabbits were assigned to one of three groups. Groups 1 and 2 were subjected to one hour of in situ right hilar occlusion followed by 2 hours of reperfusion. Group 3 was subjected to identical surgical dissection but the right hilum was never occluded. Group 1 rabbits received saline solution (1 mL/kg) before hilar occlusion and group 2 rabbits, monoclonal antibody 60.3, a blocking antibody for the CD18 adhesion molecule on the neutrophil surface (2 mg/kg). In 3 of the antibody-treated rabbits, flow cytometry was performed on blood neutrophils before and after administration of the antibody and 120 minutes after reperfusion. RESULTS: The rabbits in groups 1 and 2 had significantly increased alveolar neutrophil infiltrate and increased pulmonary vascular resistance compared with the rabbits in group 3. However, there was no significant difference between group 1 (saline solution treated) and group 2 (antibody treated). Antibody treatment did not block migration of neutrophils into the alveoli. Flow cytometry of circulating neutrophils demonstrated that CD18 was upregulated after reperfusion and that CD18 was fully blocked after antibody treatment for the duration of the study. CONCLUSIONS: We conclude that a 1-hour period of warm ischemia followed by reperfusion results in upregulation of CD18 but that emigration of the neutrophils into the alveoli is not CD18 dependent in this injury.

Animals↗
PubMed1995

Group B streptococci (GBS) injure lung endothelium in vitro: GBS invasion and GBS-induced eicosanoid production is greater with microvascular than with pulmonary artery cells.

Neonatal group B streptococcal (GBS) sepsis and pneumonia cause lung endothelial cell injury. GBS invasion of the lung endothelium may be a mechanism for injury and the release of vasoactive eicosanoids. Pulmonary artery endothelial cells (PAEC) and lung microvascular endothelial cells (LMvEC) were isolated from neonatal piglets and were characterized as endothelial on the basis of morphology, uptake of acyl low-density lipoprotein, factor VIII staining, and formation of tube-like structures on Matrigel. PAEC and LMvEC monolayers were infected with COH-1 (parent GBS strain), isogenic mutants of COH-1 devoid of capsular sialic acid or all capsular polysaccharide, or a noninvasive Escherichia coli strain, DH5 alpha. Intracellular GBS were assayed by plate counting of colony-forming units resistant to incubation with extracellular antibiotics. All GBS strains invaded LMvEC significantly more than PAEC, showing that the site of lung endothelial cell origin influences invasion. DH5 alpha was not invasive in either cell type. Both isogenic mutants invaded PAEC and LMvEC more than COH-1 did, showing that GBS capsular polysaccharide attenuates invasion. Live GBS caused both LMvEC and PAEC injury as assessed by lactate dehydrogenase release; heat-killed GBS and DH5 alpha caused no significant injury. Supernatants from PAEC and LMvEC were assayed by radioimmunoassay for prostaglandin E2 (PGE2), the stable metabolite of prostacyclin (6-keto-PGF1 alpha), and the thromboxane metabolite thromoxane B2. At 4 h, live COH-1 caused no significant increases in eicosanoids from both PAEC and LMvEC. At 16 h, live COH-1, but not heat-killed COH-1, caused a significant increase in 6-keto-PGF1 alpha greater than PGE2 from LMvEC, but not PAEC. We conclude that live GBS injure and invade the lung microvascular endothelium and induce release of prostacyclin and PGE2. We postulate that GBS invasion and injury of the lung microvasculature contribute to the pathogenesis of GBS disease.

Animals↗
PubMed1995

Expression and function of galectin-3, a beta-galactoside-binding lectin, in human monocytes and macrophages.

A family of beta-galactoside-binding animal lectins has recently been designated as galectins. One member of this family, galectin-3, has been known as epsilon BP for its IgE-binding activity and as Mac-2, a macrophage surface antigen, CBP35, CBP30, L-29, and L-34. Although much information has accumulated on the expression of this lectin in murine macrophages and human monocytic cell lines, little is known about the expression and function of this protein in normal human monocytes/macrophages. We now report that galectin-3 is expressed in normal human peripheral blood monocytes and its level increases dramatically as human monocytes differentiate into macrophages upon culturing in vitro. Immunoblot analysis showed that there was a 5-fold increase in the level of galectin-3 after 1 day of culture and greater than a 12-fold increase after 5 days. Immunocytochemical analysis confirmed this progressive increase of galectin-3 expression in cultured monocytes. Immunogold cytochemistry/electron microscopy analysis revealed that galectin-3 was expressed on the surface of human monocytes and that the level of cell surface galectin-3 increased progressively as these cells differentiated into macrophages. The level of galectin-3 in human monocytes/macrophages was modulated by stimuli such as lipopolysaccharide and interferon-gamma, and galectin-3 was secreted when monocytes were stimulated by calcium ionophore A23187 Soluble galectin-3 caused superoxide release from human monocytes; this activity was dependent on the lectin property of galectin-3, as it was inhibitable by lactose. Thus, galectin-3 may modulate the function of this cell type in an autocrine or paracrine fashion through binding to cell surface glycoconjugates.

Animals↗
PubMed1995

Deposition of particles in the lungs of infant and adult rats after direct intratracheal administration.

The study of neonatal pulmonary defense mechanisms has been limited by difficulty in administering foreign material into the lungs of newborn animals. We have developed and standardized a simple method for the intratracheal instillation of particles into the distal airways of newborn rats. We used this method to compare intrapulmonary particle deposition in neonatal and adult rats. We instilled 51Cr-labeled microspheres (11 microns diameter) by direct intratracheal inoculation into the lungs of neonatal (< 2- or 19-h-old) and adult (6-week-old) Sprague-Dawley rats. Immediately after microsphere instillation, the lobar distribution of the particles was analyzed by scintillation counting. The anatomic location of the particles was determined by autoradiography. The instilled microspheres reached all lobes in both lungs of neonatal and adult rats. The pattern of distribution in the right lung was nearly identical in the neonatal and adult rats. In the left lung, however, particles deposited preferentially in the cranial lobe in neonates but in the caudal lobe of adult rats. Analysis of the location of particle deposition in the lungs indicated that 64% +/- 6.85 (n = 4) reached the distal airways in the neonates vs. 85% +/- 3.3 (n = 6) in the adults, whereas the remainder deposited in the conducting airways. This method provides an effective means of delivering particles into distal airspaces of neonatal rats and can be used to study pulmonary defense mechanisms in newborn animals.

Animals↗
PubMed1994

Toxoplasma gondii alters eicosanoid release by human mononuclear phagocytes: role of leukotrienes in interferon gamma-induced antitoxoplasma activity.

Toxoplasma gondii tachyzoites markedly alter the profile of eicosanoids released by human mononuclear phagocytes. Freshly isolated, 2-h adherent human monocytes release both cyclooxygenase (e.g., thromboxane [TX] B2, prostaglandin [PG] E2) and 5-lipoxygenase (e.g., leukotriene [LT] B4, LTC4) products of arachidonic acid metabolism after stimulation by the calcium ionophore A23187 or ingestion of opsonized zymosan particles or heat-killed T. gondii. However, after incubation with viable T. gondii, normal and chronic granulomatous disease monocytes release only the cyclooxygenase products TXB2 and PGE2 and fail to form LTB4, LTC4, or other 5-lipoxygenase products. Monocytes maintained in culture for 5 d lose this capacity to release TXB2 and PGE2 after incubation with T. gondii. T. gondii significantly inhibit calcium ionophore A23187-induced LTB4 release by monocyte-derived macrophages; heat-killed organisms do not affect this calcium ionophore A23187-induced release of LTB4. T. gondii-induced inhibition of LTB4 release by calcium ionophore A23187-stimulated monocyte-derived macrophage is reversed by interferon (IFN)-gamma treatment of the monolayers. LTB4 induced extensive damage to the cellular membranes and cytoplasmic contents of the organisms as observed by transmission electron microscopy. Exogenous LTB4 (10(-6) M) induced intracellular killing of ingested T. gondii by non-IFN-gamma-treated monocyte-derived macrophages. IFN-gamma-induced antitoxoplasma activity in monocyte-derived macrophages was inhibited by the selective 5-lipoxygenase inhibitor zileuton but not by the cyclooxygenase inhibitor indomethacin. These findings suggest a novel role for 5-lipoxygenase arachidonic acid products in human macrophage IFN-gamma-induced antitoxoplasma activity.

Adult↗
PubMed1994

Pulmonary artery occlusion and lung collapse depletes rabbit lung adenosine triphosphate.

BACKGROUND: Although the bronchial circulation has traditionally been thought to provide adequate blood flow for the lung when the pulmonary artery is obstructed, recent studies have demonstrated that pulmonary artery occlusion results in lung injury. We hypothesized that after pulmonary artery occlusion, aerobic lung metabolic function is altered. We studied the changes in the concentration of adenine nucleotides as markers of injury in the intact rabbit lung after pulmonary artery occlusion in the presence and absence of pneumothorax. METHODS: A thoracotomy was performed on the rabbits, and on occlusive microvascular clamp was placed on the left pulmonary artery. The rabbit lungs were studied after 24 h of in vivo left pulmonary artery occlusion (n = 5), 24 h of left pulmonary artery occlusion with the lung collapsed by pneumothorax (n = 6), or 24 h of lung collapse alone (n = 5). RESULTS: Adenosine triphosphate concentrations of the occluded left lung decreased dramatically at 24 h in the group with pulmonary artery occlusion and collapse (adenosine triphosphate concentration 196 +/- 32 ng/g for the left lung and 1,479 +/- 197 ng/g for the right lung; P < 0.001). There were no differences between the lungs in the rabbits undergoing occlusion alone or collapse alone. CONCLUSIONS: After pulmonary artery occlusion or lung collapse, adenine nucleotides are preserved if ventilation is continued. The increased permeability of rabbit lungs after 24 h of left pulmonary artery occlusion alone cannot be explained on the basis of depletion of high-energy phosphates. In the absence of ventilation due to lung collapse, pulmonary artery occlusion results in decreased adenosine triphosphate concentrations, demonstrating that the residual circulations (bronchial and pulmonary venous flow) are inadequate to support normal lung aerobic metabolism.

Adenosine Triphosphate↗
PubMed1994

Reduction in lung injury after combined surfactant and high-frequency ventilation.

Previous studies demonstrated that high-frequency oscillatory ventilation (HFOV) begun at birth limits the development of alveolar proteinaceous edema in premature monkeys at risk for hyaline membrane disease (HMD). We hypothesized that exogenous surfactant combined with HFOV would lead to even further reductions in edema. Twenty Macaca nemestrina monkeys were delivered at 134 d gestation (term = 168 d) and treated with either HFOV or conventional mechanical ventilation (CMV) from the first breath; modified bovine surfactant (Survanta [beractant]) was introduced into the trachea over the first few minutes of life. These animals were compared with 20 animals treated with either CMV or HFOV but without surfactant. At 6 h the lung was rapidly frozen in situ during inflation for determination of the volume fraction of alveolar edema. The combined use of surfactant and HFOV from the first breath reduced alveolar proteinaceous edema (3 +/- 1%; mean +/- SEM) from that seen with CMV alone (27 +/- 3%, p < 0.0001), CMV after surfactant (21 +/- 3%, p < 0.0001), and HFOV alone (13 +/- 3%, p < 0.015). We conclude that the use of surfactant with HFOV after premature birth is superior to either surfactant or HFOV alone in reducing lung injury during the first few hours of life. We speculate that this reduction in lung injury may reduce the incidence or severity of bronchopulmonary dysplasia.

Animals↗
PubMed1993

Effect of type III group B streptococcal capsular polysaccharide on invasion of respiratory epithelial cells.

Group B streptococcal (GBS) capsular polysaccharide is an important virulence factor, and its role in invasion of cultured respiratory epithelial cells was investigated. A type III GBS clinical isolate, COH1, and asialo and unencapsulated isogenic transposon capsule mutants of it were compared in an in vitro invasion assay. The results demonstrated that capsule attenuated the invasion process. Invasion was not affected when the A549 epithelial cells were preincubated with purified type III GBS capsular polysaccharide. Polyclonal type III GBS capsule antibody inhibited invasion by COH1 but did not affect invasion by the capsule mutants. Serotypes Ia, Ib, Ia/c, II, and III all invaded respiratory epithelial cells but demonstrated some strain variation in magnitude of invasion. These observations led us to conclude that type III capsular polysaccharide was not essential for invasion of respiratory epithelial cells by GBS and that bacterial factors other than capsule were responsible for respiratory epithelial cell invasion.

Bacterial Toxins↗
PubMed1993

Group B streptococci invade endothelial cells: type III capsular polysaccharide attenuates invasion.

Group B streptococci (GBS) are the most common cause of neonatal sepsis and pneumonia. The pathogenesis of GBS disease is not completely defined. GBS-induced endothelial cell injury is suggested by histological findings at autopsy and in animal studies. We hypothesized that (i) type III GBS (COH-1) invade and injure human umbilical vein endothelial (HUVE) cells and (ii) isogenic mutations in GBS capsule synthesis would influence HUVE invasion. Confluent HUVE monolayers were infected for 0.5, 2, or 6 h. Media with penicillin plus gentamicin were added and incubated for 2 h to kill extracellular bacteria. Cells were washed and lysed, and the number of live intracellular bacteria was determined by plate counting. COH-1 invaded HUVE cells in a time-dependent manner at levels 1,000-fold higher than those of the noninvasive Escherichia coli strain but significantly lower than those of Staphylococcus aureus. There was no evidence for net intracellular replication of GBS within HUVE cells. COH-1 infection of HUVE cells caused the release of lactate dehydrogenase activity. GBS invasion was inhibited by cytochalasin D in a dose-dependent manner; GBS-induced lactate dehydrogenase release was attenuated by cytochalasin D. The isogenic strains COH 1-11, devoid of capsular sialic acid, and COH 1-13, devoid of all type III capsule, invaded HUVE cells three- to fivefold more than the parent COH-1 strain. The type III capsular polysaccharide and particularly the capsular sialic acid attenuate GBS invasion of HUVE cells. Electron micrographs of lung tissue from a GBS-infected newborn Macaca nemestrina also showed GBS within capillary endothelial cells. We conclude that endothelial cell invasion and injury are potential mechanisms in the pathogenesis of GBS disease.

Cells, Cultured↗
PubMed1993

Lung mast cells increase in number and degranulate during pulmonary artery occlusion/reperfusion injury in dogs.

The role of mast cells in pulmonary artery occlusion/reperfusion injury was examined. Lung tissue was obtained from dogs after left pulmonary artery occlusion for 48 h (n = 5) or after similar occlusion followed by 4 h of reperfusion (n = 11). By light microscopy and morphometry, the percentage of mast cells increased 2.4-fold (p < 0.05) in nonoccluded right lungs and 2.9-fold (p < 0.05) in occluded left lungs without reperfusion compared with that in control lungs. After reperfusion, the occluded left lung contained 1.8-fold (p < 0.05) as many mast cells as the nonoccluded right lung and 4.2-fold (p < 0.05) more than that in control lungs. Hydroxyurea did not significantly affect the number of mast cells observed in the right and left lungs after ischemia/reperfusion; 39.8% and 54.4% of the mast cells were degranulated in nonoccluded right lung and occluded left lung preparations, respectively, after left pulmonary artery ischemia/reperfusion (each, p < 0.05 compared with control lungs). The release of eicosanoids into the airways during ischemia/reperfusion injury was also examined. Thromboxane B2 and leukotriene B4 were markedly increased (each, p < 0.05 compared with that in control lungs) in bronchial lavage fluids from both nonoccluded and occluded lungs compared with sham-occluded lungs. Thus, mast cell recruitment and degranulation may play a role in lung ischemia/reperfusion injury.

Animals↗