PubMed Health⌕ Search

Biomedical subjects

J R Hoidal

Publications and source records attributed to J R Hoidal.

At least 127 records · Page 7Linked to original sources
PubMed1982

Lung fibrosis and emphysema: divergent responses to a common injury?

Cadmium chloride, administered intratracheally to golden Syrian hamsters, causes an acute lung injury which evolves into a lesion with functional and morphological features of diffuse fibrosis. With simultaneous feeding of a lathyrogen, beta-aminoproprionitrile, this same injury evolves into functional and morphological changes of bullous emphysema. These results suggest that the same lung injury might result in either fibrosis or emphysema, connective tissue synthesis during the healing phase being the critical determinant.

Aminopropionitrile↗
PubMed1982

Potential mechanism of emphysema: alpha 1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity.

The elastase inhibitory capacity per mg of alpha 1-proteinase inhibitor (alpha 1 PI) was measured in the bronchoalveolar lavage (BAL) fluid from 26 healthy smokers and 24 nonsmokers. Activity was decreased by 40% in smokers' BAL fluid compared to nonsmokers. This effect was demonstrable by using human neutrophil elastase as well as porcine pancreatic elastase as test enzyme (elastase, EC 3.4.21.11) and was reproducible when selected individuals in each group underwent lavage on repeated occasions. In contrast, the functional activity of alpha 1-antichymotrypsin was not decreased in smokers' BAL fluid. Crossed antigen-antibody electrophoresis confirmed that inactivation of alpha 1 PI was responsible for the decrease in the elastase inhibitory capacity of smokers' BAL fluid. alpha 1 PI purified from smokers' BAL fluids contained methionine sulfoxide (4 mol/mol of inactive alpha 1 PI), whereas alpha 1 PI from nonsmokers' BAL fluid did not. Smokers' alpha 1 PI was indistinguishable from nonsmokers' alpha 1 PI on the basis of electrophoretic mobility, molecular weight, and immunoreactivity. Thus, oxidation of methionine residues in lung alpha 1 PI is associated with cigarette smoking. Because chemical oxidation of alpha 1 PI in vitro causes loss of its elastase inhibitory activity, the present observations suggest that methionine oxidation may also be the cause of decreased functional activity of lung alpha 1 PI in smokers. Oxidative inactivation of alpha 1 PI in the lungs of cigarette smokers may play a role in the development of pulmonary emphysema in this group.

Adult↗
PubMed1982

Opsonic requirements for the uptake of Cryptococcus neoformans by human polymorphonuclear leukocytes and monocytes.

Chemiluminescence was used to determine opsonic requirements for interaction of Cryptococcus neoformans with human peripheral blood polymorphonuclear leukocytes (PMNLs) and monocytes (MNs). Peak chemiluminescence (mean +/- SD) was 172 +/- 25 X 10(3) for PMNLs and 50 +/- 13 X 10(3) for MNs with 20% pooled normal human serum vs. 10 +/- 3 X 10(3) for PMNLs and 6 +/- 1 X 10(3) for MNs without serum (P less than 0.005 for each comparison). The nature of the serum requirement was investigated; alternative pathway serum complements were necessary. The alternative pathway was activated directly by C. neoformans without the need for specific antibody. Chemiluminescence provided a quantitative and reproducible assay of the interaction of human phagocytes with C. neoformans and may be useful in studying opsonic requirements of other fungi.

Blood Physiological Phenomena↗
PubMed1982

Influence of subinhibitory concentrations of penicillin, cephalothin, and clindamycin on Staphylococcus aureus growth in human phagocytic cells.

After an initial 2-h incubation with phagocytic cells, the growth of surviving intracellular Staphylococcus aureus was examined in the presence of subinhibitory concentrations of penicillin, cephalothin, and clindamycin. One-tenth of the minimal inhibitory concentrations of these antibiotics markedly reduced bacterial growth in normal polymorphonuclear leukocytes. In contrast, when human alveolar macrophages were studied, no inhibition of growth was seen. Subinhibitory concentrations of these antibiotics and polymorphonuclear leukocytes acted synergistically to reduce intracellular survival of S. aureus. This synergy did not appear to be dependent upon the microbicidal potential of the leukocyte respiratory burst, since no differences were found when polymorphonuclear leukocytes obtained from patients with chronic granulomatous disease were compared with those from normal donors.

Cephalothin↗
PubMed1982

Differences in phagocytosis and killing by alveolar macrophages from humans, rabbits, rats, and hamsters.

Phagocytosis and killing by alveolar macrophages from humans, rabbits, rats, and hamsters, were compared in vitro. In the absence of serum opsonins, human alveolar macrophages could phagocytize Staphylococcus aureus Cowan I (protein A positive), but not S. aureus EMS (protein A negative) or Pseudomonas aeruginosa MN. In contrast, rabbit, rat, and hamster alveolar macrophages did not phagocytize S. aureus Cowan I or other nonopsonized bacteria. Human alveolar macrophages, but not other species, stained positively with fluorescein isothiocyanate-conjugated protein A. When opsonized bacterial were studied, phagocytosis by human, rabbit, and hamster alveolar macrophages was found to be mediated by both Fc and C3 receptors. However, only Fc receptor-mediated phagocytosis of bacteria was demonstrated for rat alveolar macrophages. Differences were also found in the kinetics of bacterial killing by alveolar macrophages from different species. Human and rabbit alveolar macrophages rapidly killed opsonized S. aureus Cowan I. However, bacterial killing by hamster alveolar macrophages proceeded at a slower rate, and rat alveolar macrophages completely failed to kill S. aureus. These significant differences in the function of alveolar macrophages from four different species emphasize the need to document the appropriateness of animal models before using them to predict the biological activities of human alveolar macrophages.

Animals↗
PubMed1982

Lung phagocyte recruitment and metabolic alterations induced by cigarette smoke in humans and in hamsters.

Cigarette smokers had an increased number of alveolar macrophages (AM) that had temporally related increases in oxidative metabolism in vitro compared with that in nonsmokers. The AM from young asymptomatic human cigarette smokers had a selective increase in superoxide anion (O2) release compared with those from nonsmokers. The AM from older smokers had a more intense, generalized enhancement of oxidative metabolism. Smoking hamsters had similar patterns of lung phagocyte recruitment and increased macrophage oxidative metabolism. The accumulation of AM within the alveolar ducts in smoking hamsters was strikingly similar to that seen in human smokers. The temporal patterns of smoke-induced changes in oxidative metabolism by AM from hamsters and humans were the same. Filtration of particulate constituents from cigarette smoke completely abrogated the distal airway inflammation and the metabolic alterations observed in smoking hamsters.

Adult↗
PubMed1982

Alterations in leukocyte oxidative metabolism in cigarette smokers.

The polymorphonuclear leukocyte (PMN) may play an important role in the pathogenesis of lung disease associated with cigarette smoking. To investigate its potential for oxidant-mediated lung injury in cigarette smokers, we studied PMN oxidative metabolism in asymptomatic cigarette smokers and nonsmoking control subjects. We found a marked increase in oxidant release in a group of cigarette smokers. After stimulation by phorbol myristate acetate, release of superoxide anion (O-2) by PMN in smokers with white blood counts (WBC) greater than 9,000 was 50% greater than in nonsmokers with similar WBC or smokers and nonsmokers with WBC less than 9,000. Abstinence from smoking did not affect the alterations in O-2 release nor did a serum factor appear responsible. The changes appeared to be part of a generalized increase in oxidative metabolism, as there was greater oxidation of glucose (1-14C) and chemiluminescence by PMN from smokers with WBC greater than 9,000. A further estimate of lung oxidant load was determined by evaluating the marginated pool of PMN. Smokers with WBC greater than 9,000 showed a 70% increase in WBC after epinephrine, and PMN oxidative metabolism remained increased in this group. This study demonstrates that cigarette smokers with elevated WBC have increased release of potentially toxic oxygen metabolites. These cigarette smokers also demonstrated increased oxidant release from the marginated PMN pool. Because leukocyte-generated oxygen metabolites are highly reactive and can cause tissue injury, these findings may have important implications in the pathogenesis of smoking-related lung disease.

Epinephrine↗
PubMed1982

Human alveolar macrophage cytophilic immunoglobulin G-mediated phagocytosis of protein A-positive staphylococci.

Human alveolar macrophages (AM) have recently been reported to ingest and kill a strain of Staphylococcus (502A) in the absence of opsonins. To further investigate the mechanism of non-opsonic recognition, we studied phagocytosis of 23 clinical and laboratory strains of S. aureus and Staphylococcus epidermidis by AM, and by blood polymorphonuclear leukocytes (PMN) and monocytes (MN). In the absence of opsonins, AM phagocytized 18 protein A-positive but not 5 protein A-negative strains of staphylococci, and the efficiency of phagocytosis directly correlated with the amount of protein A present in the bacterial cell wall (r = 0.86, P less than 0.001). Furthermore, AM rosetted around protein A-coated Sepharose beads, but not around beads without protein A. In contrast, PMN did not phagocytize nonopsonized staphylococci, and did not rosette around either type of Sepharose. MN phagocytized protein A-positive staphylococci, but much less efficiently than AM, and showed some rosetting around protein A-coated Sepharose. The nature of the AM receptor for protein A-positive staphylococci was studied. The surface of AM was positively stained with fluorescein-conjugated antibody to human IgG, but not with IgA- or IgM-specific conjugates. No such surface-immunoglobulins were detected on PMN, and MN were only weakly positive for surface IgG. Pretreatment of AM with F(ab')2 fragments specific for human IgG (anti-Fc) inhibited subsequent phagocytosis of protein A-positive staphylococci. There was no evidence that the AM surface IgG was aggregated or immunecomplexed. From these studies we conclude that human AM possess cytophilic IgG antibodies, which can function as receptors for phagocytosis of protein A-positive staphylococci.

Animals↗
PubMed1982

Filtration deformability of rabbit pulmonary macrophage.

Rabbit PAM deformability was evaluated by positive-pressure filtration through Nucleopore membranes of well-specified pore diameter. The PAM filtration method was standardized and was influenced by apparatus variations (pore size, flow rate, cell concentration), environment (temperature, pH, divalent cations, protein concentration), and differences in PAM cell volume. The influence of phagocyte function on filtration deformability was evaluated by exposing PAMs to pharmacologic and physiologic agents with somewhat exclusive influences on phagocyte physiology. Agents that interact with microfilament contractile protein (N-ethylmaleimide, cytochalasin B) altered deformability profoundly, but no effect was observed with agents interacting with microtubules (vinblastine, colchicine). Agents that cause general PAM activation (phorbol myristate acetate) or stimulate chemotaxis (F-Met-Leu-Phe) increased deformability. On the contrary, PAM deformability was not changed by phagocytosis of Staphylococcus aureus or latex beads. Pharmacologic agents that alter PAM adhesion (aspirin, indomethacin, physiologic dose hydrocortisone) or inhibit glycolysis (2-deoxyglucose) had no influence on filtration deformability. Filtration PAM deformability reflects passive whole cell rigidity, which appears to be determined by the state of polymerization of the actin-myosin microfilament complex.

Animals↗
PubMed1982

Binding of soluble immune complexes by human monocytes and pulmonary macrophages: effects of cigarette smoking.

The Fc receptor of human monocytes and pulmonary macrophages has been evaluated quantitatively by binding of radiolabeled soluble IC. On both cell types, binding was mediated by saturable surface receptors specifically inhibited by aggregated human IgG1 and IgG3. The affinity of the Fc receptor was similar on monocytes and pulmonary macrophages from nonsmokers, but macrophages demonstrated four to 13 times more surface receptors than circulating monocytes. No difference in Fc receptor binding of monocytes was observed between cigarette smokers and nonsmokers. However, pulmonary macrophages from smokers demonstrated a significantly lower Fc receptor affinity than did those of nonsmokers, although the number of Fc receptors was the same.

Antigen-Antibody Complex↗
PubMed1981

Phagocytosis, bacterial killing, and metabolism by purified human lung phagocytes.

Phagocytic and bactericidal activities of purified polymorphonuclear neutrophils (PMNs), monocytes (MNs), or alveolar macrophages (AMs) from the same individuals for Staphylococcus aureus strain 502A or Escherichia coli strain ON2 were compared in vitro. Factors that may influence these activities were evaluated. The bactericidal activity of S. aureus and E. coli of PMNs was greater than that of MNs or AMs. Two factors were identified that may account for this result. (1) The rate of phagocytosis of opsonized S. aureus and E. coli was greater by PMNs. (2) The nonmitochondrial oxygen burst after nonparticulate stimulation was much greater by PMNs. Qualitative differences in opsonic requirements for ingestion of S. aureus by PMNs, MNs, and AMs were also identified. In contrast to PMNs or MNs, phagocytosis of S. aureus by AMs was not opsonin-dependent. The results suggest that mononuclear phagocytes may adapt their opsonic requirements to facilitate uptake of S. aureus. Despite this adaptation, their bactericidal capability remains limited when compared with PMNs.

Escherichia coli↗
PubMed1981

Human fibronectin binding to staphylococcal surface protein and its relative inefficiency in promoting phagocytosis by human polymorphonuclear leukocytes, monocytes, and alveolar macrophages.

The interaction between human fibronectin and 17 strains of staphylococci was studied in an attempt to elucidate the staphylococcal cell wall component(s) involved in fibronectin binding and to determine the influence of fibronectin upon phagocytosis by three types of phagocytic cells. Purified, radiolabeled fibronectin bound to a similar degree to six laboratory strains and three fresh clinical isolates of Staphylococcus aureus; similar binding of fibronectin was found with S. aureus strains deficient in cell wall teichoic acid or clumping factor and coagulase, as well as with three strains of S. epidermidis. There was minimal binding of fibronectin to encapsulated S. aureus and to Escherichia coli. Fibronectin bound to intact cells and to a crude cell wall preparation of S. aureus H, but not to purified cell walls or peptidoglycan. Trypsinization of staphylococci prevented subsequent fibronectin binding, but binding did not correlate well with the protein A content in S. aureus cell walls. At physiological concentrations, fibronectin binding to staphylococci did not promote phagocytosis of bacteria by human polymorphonuclear leukocytes, monocytes, or alveolar macrophages. Also, depletion of fibronectin from normal human serum did not result in a measurable loss of opsonic activity for staphylococci. It is concluded that fibronectin binding to staphylococci involves a surface protein shared among strains of S. aureus and S. epidermidis, and that in comparison to C3b and IgG, fibronectin plays a relatively minor role as an opsonin for staphylococci.

Bacterial Proteins↗
PubMed1981

Altered oxidative metabolic responses in vitro of alveolar macrophages from asymptomatic cigarette smokers.

Superoxide anion (O2) release by alveolar macrophages (AM) from young asymptomatic cigarette smokers was greater than that by AM from age-matched nonsmokers. Greater O2 release by AM from cigarette smokers was observed before and after stimulation by bacteria or phorbol myristate acetate (PMA). In contrast, oxygen uptake and glucose (1(-14)C) oxidation by unstimulated or stimulated AM from cigarette smokers was the same as that by AM from non-smokers. The selective increase of O2 release by AM from cigarette smokers was not due to a lack of O2 scavenging agent within the cells, since intracellular superoxide dismutase (SOD) was increased in AM from smokers. The potential importance of enhanced O2 release by AM from cigarette smokers was confirmed by demonstrating that lysis of fibroblasts induced by AM from smokers was completely prevented by addition of SOD and catalase.

Adult↗
PubMed1981

Pulmonary inflammation due to oxygen toxicity: involvement of chemotactic factors and polymorphonuclear leukocytes.

Although the pathogenesis of pulmonary oxygen toxicity is not fully understood, the fact that increased numbers of polymorphonuclear leukocytes (PMN) are found in the lung and that these increases coincide with the massive endothelial damage raises the possibility that PMN may contribute to lung injury caused by hyperoxia. In order to begin to elucidate a mechanism for this influx of PMN, we measured the chemoattractant activity for PMN of lung lavages of rats exposed to greater than 95% oxygen for various durations. We found that the chemoattractant activity of the lavages of the lungs of rats exposed to hyperoxia for 66 h was markedly increased (9.66 +/- 1.0 times greater) compared with activities in lavages of normoxic control rats. Furthermore, these increases in chemoattractant activity in lung lavages correlated well with increases in the number of PMN (7 times greater than that in normoxic control animals) in the alveolar lavages that occurred after the rats had been exposed to hyperoxia for 66 h. These increases were followed in a few hours by the death of most of the rats (71%). These findings suggested that a close temporal relationship exists between the generation of high concentrations of chemoattractants in lung lavages, PMN influx into lung lavages, and death of rats exposed to hyperoxia. The results supported the possibility that PMN may be involved in the pathogenesis of pulmonary oxygen toxicity.

Animals↗