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Biomedical subjects

H Y Reynolds

Publications and source records attributed to H Y Reynolds.

At least 37 records · Page 2Linked to original sources
PubMed1989

Human alveolar macrophages release a factor that inhibits phagocyte function.

Human alveolar macrophages release in vitro a factor that inhibits both random migration and chemotaxis of human polymorphonuclear neutrophils (PMN). This factor is not cytotoxic and is recovered in culture supernatants of alveolar cells from most nonsmoking normal subjects. The inhibitor can be detected 30 min after cell cultures are established and is still produced after 24 h in culture. Its release was inhibited by cycloheximide. When supernatants are separated by molecular sieving (I-60 Waters HPLC column), most of the inhibitory activity is recovered in the low-molecular-weight fractions of the chromatogram (less than 1,000 D). The inhibitor has a broad spectrum of activity against known chemoattractants in that it reduces significantly the chemotaxis of PMN induced by the formyl peptide FMLP, by the complement fragment C5a, and by leukotriene B4; it also decreases the chemotactic activity associated with a monocyte-derived interleukin 1 preparation and the chemotactic activity derived from alveolar macrophage culture supernatants. The inhibitory factor is partially heat labile, is sensitive to aminopeptidase M, and is nonpolar. Both phorbol myristate acetate (PMA) and FMLP-induced superoxide release by PMN are diminished significantly in the presence of this inhibitory factor (p less than 0.01 for PMA and p less than 0.05 for FMLP). The inhibitor also reduces monocyte chemotaxis but has no effect on monocyte random migration. Finally, studies with [3H]FMLP indicate that this inhibitor does not act at the site of receptor binding on PMN. Thus, human alveolar macrophages can release in vitro both neutrophil chemotactic factors and an apparent neutrophil-inhibiting factor that may modulate positively and negatively the movement and the respiratory burst of neutrophils in the alveolar space.

Cell Movement↗
PubMed1989

Pulmonary consequences of congenital and acquired primary immunodeficiency states.

A sophisticated system of pulmonary host defense strives to maintain the functional integrity of the lung against the threats of infections, toxins, and malignancy. Congenital and acquired defects in the immune mechanisms of this host defense are associated with a variety of pulmonary disorders that include infections with usual or opportunistic organisms; inflammatory disorders; and malignancies. The age of the patient, associated abnormalities, family history, and the type of pulmonary and systemic diseases that are present provide clues to the specific underlying disorder. Laboratory tests including immunoglobulin levels, lymphocyte subset enumeration, and tests of lymphocyte function can help to confirm the clinical impression. Determination of the specific disorder allows the physician to anticipate possible complications, initiate appropriate prophylactic measures, and, in an increasing number of diseases, offer specific therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Hypersensitivity pneumonitis: correlation of cellular and immunologic changes with clinical phases of disease.

Many airborne organic antigens in the form of fungal spores and thermophilic bacteria or dander and aerosolized proteins can cause hypersensitivity pneumonitis after repeated inhalational exposure. Although a syndrome of acute illness often occurs, many people who are exposed and become sensitized can remain asymptomatic. However, immunologic evidence from an analysis of cells and antibodies obtained by bronchoalveolar lavage from asymptomatic subjects may indicate an ongoing alveolitis. With chronic illness, which has many characteristics of an interstitial fibrotic pneumonitis, a lymphocytic alveolitis and granulomatous reaction develop in the lungs. This review emphasizes the immunological changes in the lungs that occur at different phases of hypersensitivity pneumonitis and contribute to current concepts about pathogenetic mechanisms.

Adult↗
PubMed1988

Immunoglobulin G and its function in the human respiratory tract.

Immunoglobulin G--which can be subdivided into four classes, each with different functional characteristics--is an important component of the host defense system of the respiratory tract. An excessive amount can be produced or can accumulate after airway irritation (exposure to cigarette smoke) or from immunologic stimulus of B-lymphocyte-plasma cells in types of hypersensitivity and interstitial lung diseases. Specific antibody activity can be identified in organic dust-induced hypersensitivity pneumonitis and asthma that contributes to disease pathogenesis. The availability of opsonic antimicrobial antibodies is essential for optimal function of phagocytes in uptake and containment of bacteria. With an absolute or functional deficiency of IgG, recurrent and chronic types of sinopulmonary infections occur. These extremes of IgG availability, either high levels (presumably excessive) or deficient, are discussed in this review.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Bronchoalveolar lavage: clinical role and quantitative assessment.

The field of research bronchoalveolar lavage has grown exponentially in the past decade. Despite this growth, the clinical role of lavage is uncertain. The authors review the clinical areas in which lavage has made its greatest impact as a diagnostic test (e.g. eosinophilic pneumonia, eosinophilic granuloma, alveolar proteinosis, infection, and neoplasia). The importance of the test early in the evaluation of undiagnosed diffuse alveolar diseases is considered. Finally we discuss the possibility that urea marks the recovered lining fluid volume and thus serves as a standard denominator. Results from our laboratory indicate that it does not. We feel that lavage is clinically useful and should be employed in the evaluation of undiagnosed diseases. Although it has provided data about the pathogenesis of chronic inflammatory diseases, its role in the longitudinal evaluation of these illnesses remains to be proven.

Bronchoalveolar Lavage Fluid↗
PubMed1987

Histamine levels in bronchoalveolar lavage from patients with asthma, sarcoidosis, and idiopathic pulmonary fibrosis.

Bronchoalveolar lavage (BAL) has been used extensively as a research tool to elucidate immunologic events occurring in the lower respiratory tract of patients with numerous diseases and, most recently, to study patients with asthma. We assessed mast-basophiloid cell numbers and histamine levels with a sensitive histamine assay, lower limit of sensitivity, 25 pg/ml, in BAL fluid from normal individuals (n = 9) and compared these results to those obtained from patients with sarcoidosis (n = 31), idiopathic pulmonary fibrosis (IPF) (n = 8), and mild asthma (n = 7). Patients with sarcoidosis demonstrated a significant increase in total BAL mast-basophiloid cells, 9.6 +/- 4.1 X 10(4), compared to total cells in normal individuals, 0.0, p = 0.03, whereas only patients with IPF had significant elevations in BAL histamine levels, 1315 +/- 737 pg/ml, versus levels in normal individuals, 161 +/- 54 pg/ml, p = 0.002. A good correlation existed between histamine levels on an aliquot of lysed BAL cells and BAL histamine levels, R = 0.655 and p = 0.02, but not with either the total number or percent mast-basophiloid cells in BAL assessed on Wright's stained cytocentrifuge preparations. Subjects with asthma had both normal numbers of BAL mast-basophiloid cells and histamine levels. These data suggest that BAL histamine levels are easily quantified, the reason(s) for elevations in BAL histamine levels in IPF need further investigation, BAL histamine levels in subjects with asthma are not elevated in those with mild and stable disease, and lumenal mast-basophiloid cells are one major source of BAL histamine.

Adult↗
PubMed1987

Lung inflammation: normal host defense or a complication of some diseases?

The inflammatory response in lung tissue is an important part of host defense that aids in removing microorganisms or particles that have reached the distal airways and alveolar surface. It augments the usual function of alveolar macrophages, immunoglobulins, and other defense mechanisms such as mucociliary clearance. However, excessive or poorly regulated inflammation can be destructive of tissue, thus contributing to many disease processes that can lead to fibrosis and impaired gas exchange. Several examples of diseases that feature inflammation as part of their pathophysiology have been selected for this review; i.e. asthma (especially examining the late-phase reaction that involves PMNs), chronic bronchitis (in which irritants and bacterial products may stimulate mucus secretion and inflammatory cells), interstitial lung diseases (IPF may disclose PMNs but sarcoidosis and hypersensitivity pneumonitis feature collections of activated lymphocytes), and acute lung injury leading to adult respiratory distress syndrome (PMNs and their breakdown products and enzymes incite local destruction of alveolar tissue). In preparation for these disease examples, a thorough review of the normal interactions between alveolar macrophages, various opsonins, complement and chemotactic factors, and the responsiveness of PMNs is given first.

Asthma↗
PubMed1987

Bronchoalveolar lavage.

In formulating a reasonable position about the clinical use of BAL and its analysis, one must acknowledge that it is still an experimental procedure that needs further assessment, and it must continue to be included as part of patient research protocols. Therefore, neither the patient nor his/her insurance carrier should foot the bill, yet. The cost involved in analysis of BAL fluid and serum raises another consideration about how many things need to be measured and what tests give the essential information and are the most discriminating. Clearly, all of the assays suggested by some of the BAL results given in table 2 are not necessary. The cell count and the differential count, indicating the relative percentage of lymphocytes among the respiratory cells, and monoclonal antibody staining to distinguish the various T-cell subtypes give most of the essential cell information that relates to activity of alveolitis and to diagnosis in the interstitial lung diseases. Finding a very high percentage of lymphocytes in BAL fluid shifts the differential diagnosis in an unknown diffuse interstitial lung disease to the possibility of a granulomatous process, especially sarcoidosis or hypersensitivity pneumonitis; whereas elevated PMN with about 3% eosinophils also present suggests possible idiopathic pulmonary fibrosis. Many of the protein and enzyme assays have a role in describing immunopathogenesis, but are rarely measured until a few days after the procedure. Some quite sophisticated cell mediators can be measured, such as interleukin-2 produced by helper T-lymphocytes and many macrophage effector substances that may give more precise information than just cell counts and various immunoglobulin values. These assays require complex biochemical and cell culture work and are only available in special research laboratories, limiting the availability of such tests. Thus, it is not easy to suggest just what tests should be conducted with BAL cells and fluid to tailor costs yet give comprehensive clinical information, too. The use of BAL to obtain cells and proteins lining the alveolar space in many ways is still in its infancy, and new applications are being sought for a substantial list of lung diseases. Just the tip of the iceberg has been investigated, and much more may remain to be uncovered.

Bronchi↗
PubMed1987

Limitations of using urea to quantify epithelial lining fluid recovered by bronchoalveolar lavage.

The quantitation of substances in the epithelial lining fluid (ELF) of the lower respiratory tract, as obtained by bronchoalveolar lavage (BAL), is not precise because of the variable dilution of the ELF by the instilled lavage fluid. It has been reported that the absolute concentration of proteins in ELF can be determined by using the ratio of urea concentration in BAL fluid to that in serum as a method to calculate the volume of ELF recovered by BAL. Furthermore, it has been suggested that the error caused by diffusion of urea into the instilled lavage fluid can be minimized by instilling only 100 ml (5 X 20 ml) of saline rather than 300 ml (6 X 50 ml). We tested the validity of this method by collecting and individually analyzing aliquots from 2 different BAL protocols--a 100-ml (5 X 20 ml) BAL and a 300-ml (6 X 50 ml) BAL--performed in 6 healthy, nonsmoking subjects. Total protein, albumin, and urea were measured in each aliquot and in pooled fluid from each BAL procedure, and urea was measured in serum. In the 300-ml BAL, total protein and albumin concentrations tended to decrease progressively from the second to the sixth aliquots. In contrast, the urea concentration increased progressively from the first to the sixth aliquots. The concentration of albumin in ELF, calculated from the concentration of urea and albumin in each BAL aliquot, tended to decrease in each successive aliquot, becoming significant by the fourth aliquot.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1987

The impact of bronchoalveolar lavage cell analysis on clinicians' diagnostic reasoning about interstitial lung disease.

To assess the impact of bronchoalveolar lavage (BAL) on clinicians' diagnostic reasoning, we administered serial telephone questionnaires to all pulmonary physicians submitting BAL specimens to our laboratory from nonimmunocompromised patients with diffuse interstitial lung disease. Questionnaires were completed when the lavage specimens were first submitted and again after the results were reported to referring physicians. We recorded the clinicians' ordered list of likeliest diagnoses for the patient, a level of confidence in each diagnosis mentioned, and any proximate plans for further diagnostic tests. Of 78 patients in the study, information from the BAL fluid cell analysis caused clinicians to change their diagnostic thinking in 46 (59 percent). These changes were far more frequently appropriate (52 percent) than not (9 percent), and clinically impressive changes did occur but were infrequent (3 of 78 [4 percent]) in this series. Specifically, BAL permitted the unexpected diagnosis of Pneumocystis carinii in a patient not previously suspected to have acquired immune deficiency syndrome (AIDS) and appropriately encouraged clinicians to avert planned surgical biopsies in two patients subsequently found to have sarcoidosis. These findings suggest that when used to evaluate nonimmunocompromised patients, BAL fluid cell analysis can have an important impact on clinicians' diagnostic reasoning about their patients' interstitial lung diseases.

Biopsy↗
PubMed1987

Neutrophil chemotactic activity produced by normal and activated human bronchoalveolar lavage cells.

Activated macrophages can secrete a number of mediators that can attract inflammatory cells and enhance secretion of phlogistic substances from these cells. The ultimate effect of activated bronchoalveolar lavage (BAL) cells may be fibrotic lung injury. Inasmuch as pulmonary sarcoidosis is a disease associated with spontaneous activation of macrophages and lymphocytes among BAL cells, cells obtained from patients with sarcoidosis were compared with normal cells. We report that adherent BAL cells in culture from patients with sarcoidosis (n = 21) release during a resting period in vitro more chemotactic activity for neutrophils (PMNs) than do BAL cells from normal individuals (n = 14). After density fractionation of the respiratory cells by albumin gradient, cells from high-density fractions in the group with sarcoidosis secrete more chemotactic activity for neutrophils than cells from less dense fractions. The PMN chemotactic activity spontaneously released in vitro by BAL cells from patients with sarcoidosis correlates with the percentage of PMNs recovered by BAL. Immunochemical bioassay and high-performance liquid chromatographic (HPLC) analysis of BAL cell supernatants revealed a complex pattern of chemotactic factors to be present. Generally, three peaks of chemotactic activity were noted on HPLC 1-60 separations at greater than 20 kd, 8 to 10 kd, and less than 1 kd apparent molecular weights. Significantly, interleukin-1 was present in these supernatants, whereas complement components and leukotriene B4 were absent. Sarcoid BAL cells, principally alveolar macrophages, are activated in vivo as manifested by spontaneous secretion of chemotactic factors for PMNs in vitro. Interleukin-1 and other less well characterized molecules were detected. The presence of PMNs among the lavage cells of some patients with sarcoidosis appears to be an in vivo biologic correlate of this activation. These data provide additional criteria of BAL cell activation in patients with pulmonary sarcoidosis and provide further evidence concerning factors that attract inflammatory cells into the lung.

Bronchoalveolar Lavage Fluid↗
PubMed1987

Host defense impairments that may lead to respiratory infections.

Host defense mechanisms spaced along the respiratory tree and in the alveolar spaces effectively remove or contend with micro-organisms that enter the airways, so serious lung infections occur rarely in healthy people. Special circumstances, such as virgin exposure to a virulent microbe or a large innoculum of a pathogen, can result in illness, but usually routine surveillance host defenses are protective and suffice to keep colonizing airway flora in check. When pneumonia develops or recurrent sinopulmonary infection exists, however, some element of the normal defense apparatus may have failed or is inadequate. This review highlights several components of the apparatus, that is immunoglobulins IgG and IgA and the interaction of alveolar macrophages and lymphocytes, and examines deficiencies in their function that may result in infection. Along the conducting airways, poor mucociliary clearance and/or deficiencies in certain IgG subclass antibodies or destruction of IgA may predispose to sinopulmonary infections; these may be a manifestation of a hereditary disease. In pneumonia the alveolar macrophage is positioned as the central cell which must respond in several directions. This scavenger phagocyte first intercepts the microbe and either can kill or contain it or must call in some other phagocytic cell or inflammatory mediator(s) for assistance. Opsonic antibodies (IgG) and other nonimmune opsonins (complement and surfactant or fibronectin fragments) facilitate phagocytosis, but an absence of antibody may permit infection to develop with encapsulated bacteria (pneumococcus). Insufficient bone marrow reserves of PMNs or a paucity of chemotactic factors to attract them into the alveoli is a situation that may permit gram-negative bacilli and fungal organisms to flourish. Inability of immune T-lymphocytes to energize macrophages, through soluble cellular mediators that provide cell-mediated immunity and activation, makes containment of certain intracellular microbes impossible for these phagocytes (Legionella or mycobacteria). Likewise, concomitant infection of macrophages with viruses (human immunodeficiency virus, and cytomegalovirus or herpes viruses) plus an excessive T-lymphocyte suppressor cell influence may make P. carinii and common bacterial and fungal organisms difficult to contain in the lungs of AIDS patients. Consideration about what the lung host deficiency might be can make therapy more specific through immunization to develop special antibodies, replacement of certain immunoglobulins (IgG subclasses), or selective administration of cell mediators (gamma-interferon or interleukins).

Antibody Formation↗
PubMed1987

Bacterial adherence to respiratory tract mucosa--a dynamic interaction leading to colonization.

Normally, the mucosa of the nasooropharynx, trachea, and, perhaps, the major bronchi is colonized with aerobic and anaerobic microbes. This epithelial surface coexists with the microbial flora and is not overgrown with it. Moreover, the physiologic functions of the mucosa--including a protective barrier, mucociliary clearance and humidification, and warming of respired air--are not impeded. How this flora is controlled and what is amiss when virulent or pathogenic bacteria can cause infection are fascinating questions. A balance is maintained during health in which epithelial cell integrity--a function of proper nutrition, available secretory immunoglobulins and glycoproteins, and ciliary motion--resists the microbe's attempt to attach via specialized receptors (pili) or by proteolytic destruction of local proteins. These interactions are reviewed in detail. When colonization is excessive and aspiration of more microbes into the lower airway occurs, infection is more probable. Certain bacteria such as Streptococcus pneumoniae and Hemophilus influenzae, which are associated with chronic bronchitis, illustrate a mechanism in which the host-microbial balance may be upset by selective impairment of a host protein, secretory IgA1. Alternatively, viral infection or cilotoxic microbes (mycoplasma) can favor colonization of bacteria when mucosal clearance mechanisms are impaired. Last, mucosal integrity can be breached by noxious gases or inflammation that may allow bacteria entry into the submucosal that provides a nidus for infection.

Animals↗
PubMed1987

Identification and rôle of immunoglobulins in respiratory secretions.

The airway surface mucosa begins in the naso-oro pharynx and lines the conducting airways, which include the trachea, major bronchi and bronchial divisions down to the level of the respiratory bronchioles. Although sampling methods used cannot completely isolate these specific areas, analysis of immunoglobulins shows variation especially in the relative proportions of secretory IgA, IgG and IgE. The air exchange surface is samples by bronchoalveolar lavage, principally, yielding alveolar secretions that contain IgG subclasses, surfactant, etc. and a variety of respiratory cells. Several diseases illustrate abnormalities that can occur in the availability of these immunoglobulins, or in their presumed antibody functions, contributing to human diseases that have a prominent component of infection. Secretory IgA either deficient or degraded by bacterial protease (especially IgA1 form) can reduce available anti-viral antibody or perhaps promote colonization of the airways with certain microbes. IgA has a dual role. As it is an important opsonic form of antibody, selective deficiency of IgG, especially subclasses IgG, and/or IgG4, can be associated with recurrent sinopulmonary infections. Sometimes IgG (IgG4) can be increased in hypersensitivity lung diseases including asthma and orga-antigen induced hypersensitivity pneumonitis (pigeon breeders disease). Finally, cystic fibrosis, affecting the lung with persistent infection often with Pseudomonas aeruginosa, can feature degradation of IgG antibody that may create blocking fragments that impair opsonin-induced phagocytosis, or this antibody can contribute to immune complex formation. Thus, immunoglobulins (antibodies) are an important ingredient of humoral host defenses in the respiratory tract and can contribute to disease, often involving infection, if quantitative or qualitative deficiencies in them exist.

Animals↗